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Family Menispermaceae
Makabuhay
Tinospora crispa (L.) Hook.f. & Thomson

HEAVENLY ELIXIR
Fa leng teng

Scientific names  Common names
Menispermum crispum Linn. Makabuhai (Tag., Bis., Ilk.) 
Tinospora crispa (L.) Hook. f. & Thomson Makabuhay (Tag., Ilk.)
Tinospora gibbericaulis Hand.-Mazz.  Paliaban (Bis.)
Tinospora mastersii Diels  Paliahan (Bis.)
Tinospora thorelii Gagnep. Panauan (Bis.)
  Pañgiauan (Bis.)
  Pañgiauban (Bis.)
  Sañgaunau (Bag,)
  Taganagtagua (Bis.)
  Taganagtagwag (Tag., Bis.)
  Tagua (Bis.)
  Heavenly elixir (Engl)
Tinospora rumphii Boerl. is an unresolved name. The Plant List
Tinospora crispa (L.) Hook. f. & Thomson is an accepted name. The Plant List

Other vernacular names
BANGLADESH: Guloncho-ban, Golonchi.
CAMBODIA: Banndol pech.
CHINESE: Bo ye qing niu dan, Fa leng teng, Da ye ruan jinteng.
FRENCH: Liane-quinine.
INDIA: Giloya.
INDONESIA: Brotawali, Antawali, Andawali.
MALAYSIA: Akar patawali, Akar seruntum, Patawali.
MARTINIQUE: Lyann span Zeb kayenn.
THAI: Bora phet, Chung ching, Kuakhohoo (Don Daeng), Wan kab hoi yai.

Botany
Makabuhay is a climbing, dioecious vine reaching a height of 4 to 10 meters. Stems are up to 1 centimeter thick and somewhat fleshy, with scattered protuberances. Leaves are thin, ovate, 6 to 12 centimeters long, and 7 to 12 centimeters wide, with pointed and truncate or somewhat heart-shaped based, smooth and shining. Petioles are 3.5 to 6 centimeters long. Racemes are solitary or in pairs arising from axils of fallen leaves, pale green, slender, 10 to 20 centimeters long. Flowers are pale green and short pedicelled. Fruit is 8 millimeters long, in long clusters.

Additional info
- Classified in Ayurvedic medicine as a rasayana herb, meaning "circulation of the nutrient" in Sanskrit, considered to enhance longevity, promote intelligence and prevent disease. (www.prevention.com)
-
Propagated by stem cuttings or seeds. Support needed for climbing.

Distribution
- In and nearby towns in thickets, in most or all islands of the Philippines.
- Perhaps an introduced species.
- Occurs in Malaya.

Constituents
• Plant contains a bitter principle, colombine (2.22%); traces of an alkaloid; and a glucoside. Also contains a amorphous bitter principle, picroretine and traces of berberine.
• A study showed that the bitter extract of the stem does not contain an alkaloid.
• Leaves yielded picroretine, traces of an alkaloid, and a substance similar to glyzirrhizin.
• Bitter principle is glucosidal in nature.
• Study reported two alkaloids, tinosporine and tinosporidine. (Later studies failed to confirm these.)
• Study yielded two new diterpenes along with known compounds tinotufolin D and vitexilactone. (7)

• Ethanol extract of vines yielded three new diterpenoids, 2-O-lactoylborapetoside B (1), 6′-O-lactoylborapetoside B (2), and tinocrispol A (3), and nine known diterpenoids (4–12). (see study below) (28)
• Proximate analysis of stem (S) and leaves (L) yielded: protein 4.7% (L) 1.2% (S), fat 1.5% (L) 0.43% (S), carbohydrate 11.8% (L) 19.4% (S), ash 2.7% (L) 1.1% (S), moisture 79.3 (L) 77.9% (S), fiber 1.59% (L) 0.65% (S). (see study below) (37)
• Study of stems yielded four new furanoid diterpenes of clerodane types, Crispene A, B, C, and D, including one known furanoid diterpene glucoside, borapetoside E. (66)
• Phytochemical analysis revealed the presence of alkaloids, flavonoids and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. (73)

Properties
- Considered febrifuge, vulnerary, tonic, antimalarial, parasiticide, and insecticidal.
- Studies suggest cardiotonic, antioxidant, antidiarrheal, antimicrobial, antidiabetic, antiproliferative, hypolipidemic, antimalarial, antinociceptive properties.


Parts utilized
Stems and leaves.

Uses
Edibility
• The basis of a popular preparation used as cordial, tonic, or ingredient in cocktails.
Folkloric
• Decoction of leaves and stems used for malaria and fever and as a tonic (40 gms to pint of boiling water).
• Scabies: Crush fresh stem and apply juice over the affected.
• Tropical ulcers and wound healing: Decoction of the stem as wash, or crush stem, soak in oil for 12 hours and apply oil extract on affected areas.
• Pounded stem, mixed with coconut oil, has been used for a variety of rheumatic and arthritic complaints; also for abdominal colic.
• Used for athlete's foot.
• Used for fertility regulation.
• Preparation with coconut oil use as cure for rheumatism; also for flatulence (kabag) in children.
• Decoction or powder form of plant used as febrifuge. Decoction of stem used as vulnerary for itches, ordinary and cancerous wounds.
• Aqueous extract used for treatment of stomach trouble, indigestion, and diarrhea.
• Rheumatism and flatulence: mixture of the vine with oil. Cut 100 gms of the vine in small pieces, mix with 3 ounces of coconut oil. Place in bottle and "cook" under the sun for 5-7 days.
• For stomach ulcers: stem is pounded inside a plastic bag, water is added, strained, and drank once daily. Also, stems are dried, thinly sliced, decocted, then drank.
• Used by nursing mothers to assist in weaning infants off breast-feeding. The bitter juice of the stem is applied to the nipple area causing the infant's aversion to breast-feeding and facilitating transfer to breast feeding.
• Internally, used as tonic and antimalarial; externally, as parasiticide.
• In Malaysia, extract taken orally to treat hyperglycemia. Also, used for treatment of malaria.
• In Thailand, wood decoction used for diabetes, fever and to reduce thirst; also used as appetizer.
• In Thai folk medicine, cold infusion of seed used to treat intoxication caused by drugs or alcohol. Infusion of stem drunk as vermifuge. Decoction of stem used to wash aching eyes and syphilitic sores. Crush leaves applied to wound and made into dressing for itches. In Indonesia, used for treatment of diabetes, hypertension and backache. In Bangladesh, juice from macerated stems used used for prevention of intestinal disorders. (73)

Others
• As pesticide (rice blackbugs, rice green leafhoppers, rice stem borers) using pounded chopped vines stirred in one liter of water and sprayed on seedlings before transplanting or soaking the seedlings overnight before transplanting.
• Makabuhay, with madre de cacao and hot red pepper extract in water sprayed on rice plants at weekly intervals.
New applications
- Being studied for it possible stimulant effect on the immune system. Anecdotal benefits for a variety of HIV-related complaints.
Recent uses and preparations
• Used Preparation of ointment: Wash and chop 1/2 glass of stem. Sauté chopped stem on low fire for about five minutes in one glass of coconut oil. Remove the stems then add half a glass of grated white candle wax. When the wax is melted, pour
into clean bottle and label. Use the ointment over the whole body, save the face area, for three consecutive nights.

Caution
Should not be used by pregnant women. Some caution use by patients with cardiac disorders.



Studies

Hay Fever / Allergic Rhinitis: A study in the Indira Ghandi Medical College showed it effective in relieving symptoms of hay fever or allergic rhinitis. The study used the supplement Tinofend 300 mg three times a day.
Anti-scabies: Tinospora rumphii Boerl. (Makabuhay) in the Treatment of Scabies: The study established the acaricidal property of Tinospora rumphii. A concomitant antimicrobial action could not be ruled out.
Furanoid Diterpenes: Study yielded cleordane type furanoid diterpenes: a new rumphioside I and known borapetodies C and F, plus three other compounds. (6)
Clerodane Diterpenes:
Study yielded two new diterpenes (1 and 2) from the leaves of Tinospora rumphii, along with known compounds tinotufolin D and vitexilactone. (7)
Swine Diarrhea Control: Study showed reduction of diarrhea with use of 25% fresh makabuhay decoction from day 15-35 in piglets with diarrhea. (8)
Antifertility Effect: Study on Sprague-Dawley rats investigated the effect of T rumphii on the activity of 3-B-hydroxysteroid dehydrogenase activity in the ovary. (9)
Hypoglycemic / Hypolipidemic: Study on the extract of Tinospora cordifolia roots for 6 weeks resulted in a significant reduction of blood and urine glucose and lipids in serum and tissues in alloxan diabetic rats. (10)
Antimicrobial / Diterpenes: Study on chloroform extract of air-dried leaves yielded a new clerodane diterpene, B2, and known diterpenes B1, tinotufolin D (B5) and vitexilactone (B3). B2 was found to have antifungal activity against Aspergillus niger and T. mentagrophytes, and antibacterial activity against P. aeruginosa and Bacillus subtilis. (11)
Hypoglycemic / Insulinotropic Activity: Study of aqueous extract on alloxan-diabetic rats showed significant reduction of blood glucose and higher levels of serum insulin levels. The insulinotropic effect was also evident in perfused human and rat islets and HIT-T5 B cells. Results suggest the hypoglycemic effect is associated with increased insulin secretion. (14)
No Diabetic Benefits / Human Study: Study of dry powder capsule of Tinospora crispa in healthy and type 2 diabetic patients showed no effect on serum glucose and insulin levels. The result was inconsistent with other studies in animal model and metabolic syndrome subjects. (1
5)
Anti-TNF-a / Prevention of Atherosclerosis-related Cardiovascular Diseases: Study investigated an aqueous and methanol extract on Tumor Necrosis Factor induced inflammation on Human Umbilical Vein Endothelial cells in vitro. Results showed T. crispa extracts have an inhibitory effect in vitro on the levels of inflammation signaling molecules and may have potential in the development of nutraceuticals for the prevention of atherosclerosis-related cardiovascular diseases. (16)
Toxicity Study / Hepatic and Renal Toxicity / Prolonged Use Concern: Results of chronic toxicity study of ethanolic extract of Tinospora crispa showed hepatic and renal toxicity potential in rats. Results suggest prolonged use of high doses of T. crispa in humans should be avoided or discontinued immediately if signs of liver or renal toxicities occur while using T. crispa. (17)
Antimicrobial / Cytotoxicity / Antioxidant: Various extracts showed very significant cytotoxicity on brine shrimp lethality bioassay. Strong antioxidant activity was seen on DPPH assay. A chloroform soluble fraction of the methanolic extract showed significant activity against tested organisms on antimicrobial screening. (18)
Borapetoside C / Improved Insulin Sensitivity: Study isolated the hypoglycemic actions of borapetoside C isolated from T. crispa. Results showed borapetoside C can increase glucose utilization, delay the development of insulin resistance and enhance insulin sensitivity. (19)
Antioxidative / Antiatheroslcerosis: Study investigated the effect of T. crispa stem aqueous extract in hypercholesterolemic-induced rabbits. Results showed improvement in lipid profile (decreased total cholesterol, triglycerides, LDL, and increased HDL). Extract also showed strong antioxidative properties and markedly reduced atheroslcerotic lesion formation. Results suggest a potential for incorporation of T. crispa as part of therapeutic regimens in the prevention of atherosclerosis. (20)
Hepatotoxin Concerns / Contrasting In Vitro Vs In Vivo Study Results / Thioacetamide Toxicity: Study evaluated the effect of an ethanolic extract of dried stems of T. crispa in a male rat model of hepatic fibrosis caused by the hepatotoxin, thioacetamide. Results showed a significant increase in the activity of liver enzymes. Although previous in vitro study showed the extract had strong antioxidant activity, this in vivo study establishes the extract contains hepatotoxins different from compounds with antioxidant properties. Study suggests reliance on data from in vitro methodologies may lead to erroneous conclusions. (21)
Antioxidative / Anti-Proliferative: Study evaluated the cytotoxicity potential and antioxidant activity of various extracts. A methanol extract showed the highest flavonoid and phenolic content, with highest scavenging activity in a dose-dependent manner. T. crispa also showed dose-dependent antiproliferative activity against many types of cancer cells. (22)
Cardiotonic / Cycloeucalenol and Cycloeucalenone: Study isolated two triterpenes from the stems, namely, cycloeucalenol and cycloeucalenone. Results showed mild cardiotonic effects: cycloeucalenol slightly increased right atrial force contractions and reduction in left atria of rat in vitro, while cycloeucalenone showed slight change from control on right and left atrial force. (23)
Borapetol B / Antidiabetic: Study evaluated the antidiabetic properties of borapetol B (C1) isolated from T. crispa in normoglycemic and spontaneous type 2 diabetic rats. Results showed 2-fold increase in plasma insulin levels in treated rats. C1 dose-dependently increased insulin secretion in isolated islet cells. Results suggest borapetol B has antidiabetic effects due to its stimulation of insulin release. (25)
Antimalarial / Plasmodium berghei / Stem: Study evaluated the antimalarial activity of T. crispa methanol extract of dried stem powder against P. berghei infection in mice. The crude extract exhibited dose-dependent antimalarial activity with strong inhibitory effect when used in combination with pyrimethamine. (26)
Anti-MRSA Activity: Study evaluated the antibacterial effect and interaction between Tinospora crispa and S. mahagoni extracts against Methicillin-resistant strains of S. aureus (MRSA). Both extracts were effective against MESA strains. However, no interaction or synergism was found in the two-plant combination. (27)
Hypoglycemic Diterpenoids / Borapetoside C: Study of EtOH extract of vines yielded three new diterpenoids and nine known diterpenoids. Compounds 4-6 (borapetosides A-C) were examined for in vivo hypoglycemic activities. Results showed significant lowering of plasma glucose levels in normal and STZ-induced type 1 diabetic mice. Borapetoside C exhibited a hypoglycemic effect with increased peripheral glucose utilization and reduced hepatic gluconeogenesis. (see constituents above) (28)
Immunomodulatory / Antioxidant / Cordioside, Quercetin, Eicosenoic Acid, Boldine / Stems: Study evaluated the immunomodulatory effect of T. crispa. Findings showed T. crispa had higher antioxidant potential than ascorbic acid. T. crispa exhibited an immunomodulatory effect through stimulation of INF-γ, IL-6, and IL-8 expressions. The immunomodulatory effect might be due to cordioside, quercetin, eicosenoic acid (paullinic acid) and boldine isolated from the T. crispa fraction isolated by LC-MS phytoanalysis. (29)
Effect on Blood Pressure and Heart Rate / Stems: Study evaluated the effects and mechanism of action of an n-butanol extract of stems on blood pressure and heart rate in anesthetized rats. Findings suggest T. crispa possesses at least three different cardiovascular-active components that act via (1) ß2-adrenergic receptors to cause a decrease in blood pressure, and ß1 - and ß2 -adrenergic receptors to cause an increase in heart rate, (2) α-adrenergic receptors to cause an increase in blood pressure and heart rate, and (3) a non-adrenergic and non- cholinergic pathway to cause a decrease in MAP and heart rate. (
30)
Alpha-Glucosidase Inhibitory Activity of Endophytic Actinomycetes: Study isolated and selected alpha glucosidase inhibitor-producing endophytic actinomycetes from various diabetic medicinal plants. Of fourteen studied plants, the highest inhibition activity to alpha-glucosidase was shown by BWA65 found from Tinospora crispa. Production of alpha-glucosidase inhibitor compounds in the plant was largely due to the contribution of actinomycetes endophytes. Findings suggest any plant can contain several endophytic microbes that can produce compounds or secondary metabolites. (
31)
Antimetastatic / Head & Neck Squamous Cell Carcinoma Cell Line: Study investigated the effect of T. crispa extract on matrix metalloproteinase-13 (MMP-13) expression and cell migration. Findings suggest T. crispa could be considered a potential therapeutic drug to prevent metastasis of HNSCC (head and neck squamous cell carcinoma). (
32)
Anti-Atherogenic / Antioxidant: Study evaluated the lipid lowering and antioxidant effects of T. crispa in rabbits fed with a high cholesterol diet. Results suggest the supplementation with T. crispa extract can reduce or retard the progression of atherosclerotic plaque development induced by high cholesterol diet. The antiatherogenic effect could be due to enhanced serum HDL, increase antioxidant status and flavonoid composition. (
33)
Wound Healing / Stem: Study evaluated the effect of Tinospora crispa on wound healing in diabetic albino mice given intraperitoneally and with local ointment application. Results showed potential benefits as remedy for diabetic wound healing, possibly through reduction of blood glucose level and prevention of microbial infection in the affected area. The addition of the ointment did not significantly contribute to wound healing with regards wound healing time and percent wound contraction. (
35) Study evaluated a methanol and chloroform extract of stems of T. crispa for healing efficiency on excision wound model in albino rats. The methanol and chloroform fractions showed significant wound healing effect comparable with standard drug use. The methanol fraction ointment showed greater activity than the chloroform fraction. (48)
Protective Against Malaria-Induced Renal Damage and Hemolysis / Stem: Study of Tinospora crispa stem extract showed protective effects on renal damage and hemolysis during Plasmodium berghei infection. Potent antioxidant activity of the extract may play a central role in protecting against oxidative stress induced by malaria. T. crispa stem extract has also been reported to have antimalarial activity against P. yoelii infection in mice. (
36)
Antiproliferative / Stem: Study evaluated the antioxidant and anti-proliferative activity of aqueous crude extract of T. crispa stem. No significant toxicity was recorded, with IC50 value of more than 1000 µg/ml. Extract exhibited moderate anti-proliferative activity on selected human cancer cell lines (IC50 MCF-7 107 µg/ml, HeLa 165 µg/ml, Caov-3 100 µg/ml, and HepG2 165 µg/ml. (see constituents above)  (
37)
No Benefit as Additional Treatment in T2 Diabetes / Clinical Trial: A randomized double-blind placebo controlled trail evaluated the efficacy of T. crispa as additional treatment in patients with T2 diabetes mellitus who did not respond to oral hypoglycemic drugs and refused insulin injection therapy. Results showed no antidiabetic benefit. Patients on T. crispa had significant weight reduction and cholesterol elevation. Moreover, study suggests an increased risk of hepatic dysfunction with T. crispa treatment supplementation. (
38)
Antimicrobial / Roots: Study evaluated various extracts of roots of T. crispa for in vitro antimicrobial activity against gram positive bacterial strains of Streptococcus pneumonia, gram negative strains of E. coli, and fungal strains of Candida albicans. A methanol extract exhibited moderate zone of inhibition against the bacterial strains used. An ethanol extract showed maximum inhibition against growth of Candida albicans. (
39)
Antioxidant / Stem: Study evaluated the antioxidant activity of T. crispa. Stem extract showed high antioxidant activity in the following order: DPPH > reducing power > metal chelating,98.8%, 0.957, 81.97%, respectively. The high antioxidant activity was attributed to apigenin and magnoflorine. There was high correlation with total phenolic content and DPPH free radical scavenging activity of T. crispa.      (
40)
Hepatoprotective / Thioacetamide Hepatotoxicity: Study evaluated an ethanolic extract of dried stems of T. crispa in a male rat model of hepatic fibrosis caused by the hepatotoxin, thioacetamide. (
41)
Mechanisms of Anti-Hyperglycemic Action / Review: The mechanisms of anti-hyperglycemic actions are due to stimulation of insulin secretion, enhancement of glucose utilization in peripheral tissues and reduction of hepatic gluconeogenesis. Borapetoside A and C are active ingredients for lowering plasma glucose. In human studies, the anti-hyperglycemic effect shown in metabolic syndrome is not evident in type 2 diabetes mellitus. (
42)
Hepatoprotective in Malarial Infection: One of the major causes of death in malaria is organ damage to the liver. In the study, liver damage during malarial infection was evidenced by significant (p<0.05) increase in AST and ALT with markedly increased albumin. Study in mice showed T. crispa extract exhibited hepatoprotective effect during malarial infection. at dose of 500 mg/kg. (
43)
Anti-MRSA Activity / No Synergism with S. mahagoni: Study showed the extracts of T. crispa and S. mahagoni were effective against MRSA (methicillin-resistant Staphylococcus aureus) strains. However, the combination of the two plants showed no synergism against MRSA strains. (
44)
Antimalarial / Plasmodium yoelii: Study evaluated the in vivo antimalarial effect of crude extract of Tinospora crispa in mice inoculated with Plasmodium yoelii. Results showed dose-dependent anti-malarial effect. (
45)
Antimalarial / Plasmodium falciparum / Stem: Study evaluated the anti-plasmodial activity of T. crispa stem extract against P. falciparum 3D7 strain in vitro. Results showed anti-plasmodial activity with IC50 between 0.27 mg/ml and 0.29 mg/ml. The effective dose to inhibit growth of P. flaciparum 3D7 strain is 2.0 mg/ml. The reduction in parasitemia degree of 3D7 strain suggests a potential candidate as antimalarial. (
54)
Enhancement of Glucose Transport: Study evaluated the effect of water-ethanol extract of T. crispa on glucose transporter (GLUT1 and GLUT4) and AMPK alpha1 and PPAR gamma expression. Results showed enhancement of glucose transport by T. crispa in L6 myotubes, mediated by the up-regulation of GLUT1, AMPK alpha and PPAR gamma expression. (
46)
Immunomodulatory Effects: Study investigated the immunomodulatory effects of a standardized 80% ethanol extract of stem on innate immune responses by evaluation of chemotaxis and phagocytic activity of neutrophils isolated from blood of male Wistar rats. Main extract ingredients were identified as syringin and magnoflorine. Results showed increased chemotactic activity of neutrophils, a dose-dependent increase in number of migrated cells and neutrophilic phagocytic activity, a dose-dependent T- and B-lymphocyte proliferation with concanavain A and lipopolysaccharide. Results suggest immunomodulatory activity and potential for use in the prevention of immune diseases. (
47)
Effect on Human Hepatocellular Carcinoma (HepG2) / Synergism with Gelam Honey Mixture: Study investigated the effect of T. crispa and Gelam (Melaleuca cajupati) honey mixture on human hepatocellular carcinoma (HepG2) and normal human hepatocytes. Results showed potent antioxidant activity and moderate antiproliferative activity against human heptocellular carcinoma cells (HepG2) depending on treatment concentration. Furthermore, the extract may improve insulin sensitizing activity, with its potential to increase expression of PY20. (
50)
Thrombolytic Activity / Gelam Honey Mixture: Study evaluated a methanol extract of stems of T. crispa for thrombolytic (in vitro clot lysis) and cytotoxic (brine shrimp lethality bioassay) activities. Results showed the stem possesses promising thrombolytic activity in vitro against human blood as well as preliminary cytotoxic activity on brine shrimp. Study suggests potential as thrombolytic medicine. (
51)
Anti-Inflammatory / Antinociceptive / Stem: Study evaluated an ethanol extract of T. crispa stem for antinociceptive (writhing and hot plate tests) and anti-inflammatory (carrageenan-induced paw edema test) activities. The extract administered intraperitoneally exhibited significant (p<0.05) antinociceptive and anti-inflammatory activities in a dose-dependent manner in all assays used. (
52)
Hypoglycemic in Metabolic Syndrome / Dry Powder Stem: Randomized double-blind placebo-controlled crossover design evaluated T. crispa dry powder in patients with metabolic syndrome. Results showed significant reduction of blood glucose from baseline. Results raised the concern of using T. crispa dry power in patients on statin with statin elevated liver enzyme. (also see: study 38) (
53)
• Review / Anti-Diabetic Effect: Review reports on the antidiabetic effect of the herb via stimulation of insulin secretion from the ß-cells and dose-dependent and time-dependent enhancement of glucose uptake in muscles. However, review cautions use of the herb because of reported hepatotoxicity. (55)
• Anti-Inflammatory / Stem: Study evaluated the anti-inflammatory properties of aqueous extract of dried stem in a rat model of carrageenan induced hind paw edema. All test concentrations (50, 100, and 150mg/kg) significantly inhibited paw edema. Activity was attributed to possible mechanisms of stabilization of cellular membranes at 5%w/v and 7/5 w/v concentrations and inhibition of protein denaturation. (56)
• Anti-Diabetic / Acute Toxicity Study / Stem: Study evaluated activities of various Thai medicinal plant extracts (T. crispa stems, A, squamosa leaves, M. sapientum flowers, and P. sarmentosum leaves) on haematological values and bioactivities in STZ-induced diabetic rats. The extracts showed no acute toxicity, with LD50>2000 mg/kg. The stem extract of T. crispa was the most effective on lowering blood glucose via increase of serum insulin. (57)
• Anti-Diabetic / Effect on Glucose Transport in Skeletal Muscle: Study investigated the effects of water-ethanol extract of T. crispa on glucose transport in a rat muscle cell-line L6 myotubes. The WETC significantly increased glucose transport activity at L6 myotubes by enhancing GLUT1 expression, a result of AMPK stimulation. (58)
• A Case of Toxic Hepatitis: Study reports on a case of toxic hepatitis related to overuse of T. crispa pellets. Report included histological assessment and analytical identification of the herbal compound, with complete recovery after discontinuation of the herbal medicine. High contents of furanoditerpenoids such as borapetosides, compounds that cause glutathione depletion and may be responsible for the hepatotoxicity. (59) Case reports of acute hepatitis caused by chronic use of high doses of T. crispa by a 49-year old male taking 10 pellets a day for chronic back pain. After two months, he presented with a jaundice and a history of dark urine, pale stools, asthenia, and right hypochondrial pain. Histopath exam was consistent with toxic hepatitis due to T. crispa. Recovery can be complete after discontinuation. (70)
Antifungal / Candida albicans / Stem Bark: Study of ethanol of stem bark of T. crispa showed antifungal activity against C. albicans (20.59%). Of five fractions obtained, fraction 1 exhibited the greatest antifungal activity (27.73%). (
49) GCMS analysis yielded 5 fractions. Fraction 1 showed antifungal activity against C. albicans with inhibitory potential of 27.73 ± 0.16%. GC-MS analysis yielded phenolic compounds, fatty acids, and terpenoids. Antifungal compounds were identified as hexadecanoic acid and 9,12-octadecadiernoic acid. (60)
• Anti-Toxoplasma gondii Activity: Study of crude extracts T, crispa and P. guajava showed high amounts of crude alkaloids and were not toxic to Vero cells (EC50>100µg/mL). T. crispa crude extract showed potential anti-T. gondii activity with EC50 of 6.24 ± 0.53 µg/mL. Alkaloids may be key to the anti-parasitic activity. (61)
• Tinocrisposide / Chemopreventive Against Human Cancer Cells: Study evaluated the cytotoxic activity of tinocrisposide extract from T. crispa against human cancer cell lines (HI299 and MCF-7 cell lines). Results showed that while it did not show any cytotoxicity against HI299 and MCF-7 cell line, it can be used as a chemopreventive agent toward those cell lines. (62)
• Artesunate-Tinospora Combination in Mouse Malarial Models: Study evaluated the effect of combinations of artesunate and T. crispa extract on nuclear factor kappa-B (NFkB) and intracellular adhesion molecule-1 (ICSAM-1) expression in brain of mouse malaria models. Results showed significantly decreased expression of NFkB and ICAM-1 with the combination group compared to either one alone. (63)
• Tinospora crispa Ointment Against Head Lice / Pediculus humanus capitis: Study evaluated the safety, efficacy, and physiochemical characteristics of T. crispa pediculicidal ointment. Results showed the ointment to be non-irritant, with a primary irritation index of 0.15, with comparable pediculicidal activity of positive control Kwell®, a 1% pemethrin shampoo. Activity was attributed to the presence of compounds moupinamide and physalin I. (64)
• Anti-Obesity and Anticancer Potential pf Gelam Honey and T. crispa: Review reports on the potential of Malay medicine practice of consumption of Gelam Honey and T. crispa herb in controlling obesity and treating cancer. In the obesity study, GH and TC significantly decreased body weight, total cholesterol, triglycerides and glucose level. In cancer studies, both were found to inhibit colon, breast, liver and lung cancer cell growth. (65)
• N-trans-feruloyltyramine / Anti-Nitric Oxide Activity / Antioxidant: Study showed the nitric oxide inhibitory activity of T. crispa extract was related to N-trans-feruloyltyramine content. Antioxidant activity of ethanolic extract showed an IC50 value of 88.56 µg/mL. (67)
• Regulation of Cholesterol Metabolism in Human Hepatoma Cancer Cell Line: Study showed the ability of T. crispa aqueous extract to regulate cholesterol metabolism in human hepatoma cancer cell line (Hep G2). The extract significantly increased (p<0.05) the concentration of Apo A1, LCAT, LDLR, SRB-1, and HL. Efficacy was good when compared with standard drug simvastatin. (68)
• Herb-Drug Interaction / Effect of T. crispa on Drug Metabolism in Rat Liver: Study investigated the in vitro and ex vivo effects of crude extract and various solvent extracts of stem on aminopyrine N-demethylase activity in Sprague-Dawley rat liver. Results showed the chloroform extract of T. crispa affected Phase 1 aminopyrine N-demethylation in certain groups of rat liver. Caution is advised with long-term extract use at doses equal to or greater than 500 mg/kg because it can significantly elevate ALT level. (6
9)
• Antiproliferative / Triple Negative Breast Cancer Cell Lines: Study of T. crispa methanol extract showed antiproliferative effect on triple negative breast cancer cells with less toxicity to the normal breast cells. Cell death was mainly due to apoptosis and the combination of T. crispa and cisplatin significantly down-regulated the NF-kB gene expression which increased apoptosis in cancer cell lines. (71)
• Larvicidal / Filarial Vector Cx quinquefasciatus / Fruit: Study of T. crispa fruit extract showed promising mosquito larvicidal potency against all instars of Culex quinquefasciatus larvae. Preliminary phytochemical analysis yielded tannin and steroid which may be responsible for the larval toxicity. (72)
• Hepatoprotective / Alloxan Induced Liver Damage: Study evaluated the hepatoprotective effect of T. crispa in alloxan induced liver damage in male wistar rats. An ethanolic extract at dose of 100 and 200 g/200gbwsignificantly reduced blood ALT and AST, along with number of pyknotic nuclei, karyorrhexic nuclei and karyolysis nuclei lower than negative control. (74)
• Preparation of Tinospora cripa Composition for Blood Sugar Reduction / Invention: This invention discloses the composition and preparation of a T. crispa medicinal preparation for blood sugar reduction from raw materials of 70-95% T. crispa and 5-30% lucid ganoderma. The process involves culture medium inoculation, crushing and drying of fresh stems, fermentation. Toxicity of T. crispa is well controlled, with high concentration of total diterpenoid compounds Rumphioside Ac-D and Borapetoside B with high reduction effect on blood sugar. (75)
• Toxic Hepatitis Induced by T. crispa / Clerodane furanoditerpenoids / Stems: Study reports on a new case of toxic hepatitis in a 57-year old male patient following consumption of two aqueous extracts of fresh Tinospora crispa stems. It differs from two previously reported cases of chronic intake of powdered dry stems in pellet and tablet formulations. LC/DAD/MS analyses of offending sample yielded a species-specific molecular marker borapetoside C (1), along with 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. Results suggest the mechanisms of underlying hepatotoxicity of T. crispa are the same as those encountered with furanoditerpenoids-containing plants i.e., Teucrium chamaedrys or Dioscorea bulbifera. In the use of T. crispa for treatment of T2DM, study suggest closer monitoring for signs of hepatotoxicity. (76)
• Antihyperglycemic Tablet Formulation / Stems: Study evaluated the anti-hyperglycemic actions of T. crispa formulated as tablet from its lyophilized extract. Water-ethanol (70:30) solvent mixture was used to extract the stems through maceration method and the anti-hyperglycemic activity of the crude extract was tested on alloxan-induced hyperglycemic Wistar albino rats. Results showed the extract had relative therapeutic effect with glibencladmise as standard drug. The end-product is a dark-brown tablet with a coffee-like aromatic odor, slightly bitter tasting, containing 500 mg of lyophilized makabuhay stem aqueous extract. (77)
• Herb-Drug Interaction / Effect of T. crispa on Drug Metabolism in Rat Liver: Study investigated the in vitro and ex vivo effects of crude extract and various solvent extracts of stem of T. crispa on aminopyrine N-demethylase activity in Sprague-Dawley rat liver. In vivo, the chloroform extract could affect the N-demethylation of aminopyrine and probably other drugs that undergo similar phase I N-demethlation reactions i.e., diazepam, morphine, etc. The ex vivo study showed significant effect on aminopyrine N-demethylase activity. Results in normal SD rats advised caution for long term intake of doses 500 mg/kg and more of the chloroform extract because of potential toxicity to the liver. (78)
• Antibacterial / Toxicity Study: Study evaluated the antibacterial activity and safety of aqueous and alcoholic extracts of T. crispa. Antibacterial activity were done by disc diffusion and broth dilution methods against clinical isolates of 8 MRSA and S. aureus ATCC strain. Disc diffusion method of ethanol extract on tested organisms showed MIC 25 mg/ml, while aqueous extract showed no effect on majority of test organisms. Acute toxicity study did not show toxicological signs in rats at higher dose of 4 g/kg ethanol extract and 2 g/kg aqueous extract. The AE showed mortality at 4 g/kg. There were significant changes in biochemical parameters. Results suggest the EE of TC is a promising anti-MRSA agent, and the LD50 was estimated greater than 4 g/kg. (79)
• Comparative Bioactivities in Diabetic Rats: Study evaluated the activities of Thai medicinal plant extracts from T. crispa stems, A. squamosa leaves, M. sapientum flowers, and P. sarmentosum leaves on hematological values and bioactivities in STZ-induced diabetic rats. The extracts (250 mg/kg) decreased blood glucose level but increased body weight of rats. The extracts had non-acute toxicity within 24 h and 14 days (LD50>2000 mg/kg) and possessed hypoglycemic, hypolipidemic, and hyperinsulinemic activities. The stem extract of T. crispa was most effective extract for lowering blood glucose level via increase of serum insulin. (80)
Sensitivity Test of E. coli Against T. crispa Extract: E. coli produces a toxic protein which can disrupt intestinal wall. Livestock react to toxins by a diarrheic response to remove toxins from the digestive system. Breeders use antibiotics freely which results in bacterium resistance to the antibiotics. An alternative is the use of brotowali (T. crispa). Study evaluates E. coli bacterium sensitivity against brotowali extract. Amoxicillin was positive control while DMSO was negative control. Results showed T. crispa at concentration of 8.0% and 32% are more sensitive than amoxicillin by measures of inhibition zone. (81)
• Anti-Proliferative on Breast Cancer Cell Lines: MCF-7 and MDA-MB-231: Study evaluated the anti-proliferative activity of water extracts of T. crispa on MCF-7 and MDA-MB-231 breast cancer cell lines with 3T3 normal fibroblast as control cell. Results showed cell viability decreased in a dose dependent manner in each cells similar to the patter of tamoxifen, with lowest IC50 in MCF-7. IC50 for MCF-7, MDA-MB-231 and 313 cells were 42.75 ± 4.61µg/ml, 46,88 ± 1.75 µg/ml and 65.50 ±4.64 ≤g/ml, respectively. (82)
• Analgesic / Stem: Study evaluated the analgesic activity of T. crispa stem extract by acetic acid induced writhing test using Swiss albino mice. At 400 mg/kbw, the crude methanol extract and fractions showed significant (p<0.05) inhibition of writhing compared to standard Diclofenac Sodium with the petroleum ether soluble fraction showing the most significant analgesic activity (51.94%) compared with standard (65.12%). Crude extract and fraction showed no significant antimicrobial activity. (
83)
• Mechanism of Apoptosis in Hepatoma G2 Cell Lines: Hepatoma G2 (HepG2) cell line proliferation is controlled by insulin-like growth factor (IGF) signaling system. Tinospora crispa contains natural insulin enhancer and possesses antiproliferative effects. Study evaluated the mechanism of T. crispa in compensating insulin resistance to induce apoptosis in HepG2 cancer cell line. Results suggest T. crispa has potential as an anticancer agent via targeting insulin-like growth factor system and insulin signaling pathway in HepG2 cancer cell line. (84)
• Cardiac Contractility Effect of Cycloeucalenol and Cyclocucalenone / Stems: Study isolated two triterpenes, cycloeucalenol (1) and cycloeucalenone (2). Cycloeucalenol slightly increased right atrial force of contraction, while showing an initial reduction followed by sustained reduction of about 10% on the left atria of rat in vitro. Cycloeucalenone showed slight change from control on right and left atrial force. Study suggests the two triterpenes produced mild cardiotonic effects. (85)
• Phytoconstituents of Solvent Extracts / Antibacterial / Stem: Hexane extract yielded alkaloids, flavonon, polyphenol substances and steroid type saponins; chloroform extract yielded alkaloids and triterpenoid type saponins; butanol extract yielded alkaloids, flavon, and polyphenol substances; aqueous extract yielded free acid and steroid type saponins; methanol extract yielded alkaloids, tanins, and triterpenoid type saponins. Hexane, chloroform, and butanol extracts showed zones of inhibition for gram-positive bacteria S. aureus with ZOI of 1.5 cm, 1.3 cm and 1.2 cm. (86)
• Lipid-Lowering / Anti-Atherosclerotic: Study evaluated the hypocholesterolemic and anti-atherosclerotic properties of T. cripa aqueous extract on hyperlipidemic rabbits for 10 weeks. Results showed lowering of total cholesterol, triglyceride, LDL-C while HDL level was elevated. There was also lowering of GGT, ALP. There was also significantly higher (p<0.05 total antioxidant status, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. Results suggest supplementation with T. crispa extract of 450 mg/kg might reduce or retard progression of atherosclerotic plaque development induced by dietary cholesterol. (87)


Availability
- Wild-crafted. 
- Capsules, extracts, supplements in the cybermarket.


Updated June 2019 / June 2018 / November 2016


Photos © Godofredo Stuart / StuartXchange
Additional Sources and Suggested Readings
(1)
Tinospora rumphii Boerl. (Makabuhay) in the Treatment of Scabies / Nelia P Salazar et al /
(2)
Stop Sneezing This Season / Sara Altshul / Prevention Sept 2007
(3)
Insecticidal use of Tinospora rhumhii
(4)
New antimicrobial diterpenes from Tinospora rumphii.
(5)

Recent uses / Philippine Inquirer. Monica Feria. Oct 6, 2007

(6)
Furanoid diterpene glucosides from Tinospora rumphii / Teresita Martin et al / Phytochemistry
Volume 42, Issue 1, May 1996, Pages 153-158 / doi:10.1016/0031-9422(95)00902-7

(7)
Clerodane Diterpenes from Tinospora rumphii / C Y Ragasa et al / J. Nat. Prod., 2000, 63 (4), pp 509–511
DOI: 10.1021/np9902946

(8)
The use of 25% fresh makabuhay (Tinospora rumphii Boerl) vine decoction as preventive medication for swine (Sus domesticus) suckling diarrhea (15-35 days old) / Carace G B and Villaver T T / CLSU Scientific Journal • Vol 1-2. pp 59-60

(9)
The modulation of ovarian 3B-Hydroxysteroid dehydrogenase activity in rats during treatment with Tinospora rumphii Boerl / Else Dapat / 1999 / DOST SciNET-Phil
(10)
Hypoglycaemic and hypolipidaemic action of alcohol extract of Tinospora cordifolia roots in chemical induced diabetes in rats / Stanely Mainzen Prince, Menon VP / Phytother Res., April 2003 17(4): pp 410-413.
(11)
New antimicrobial diterpenes from Tinospora rumphii / Cruz, Ma. Cecelyn S. / Thesis / 2000 / De La Salle University
(12)
Sorting Tinospora names / Authorised by Prof. Snow Barlow / Maintained by: Michel H. Porcher / MULTILINGUAL MULTISCRIPT PLANT NAME DATABASE / Copyright © 1997 - 2000 The University of Melbourne.
(13)
Tinospora crispa (L.) Hook. f. et Thomson (accepted name) / Chinese name / Catalogue of Life, China
(14)
The hypoglycaemic and insulinotropic activity of Tinospora crispa: studies with human and rat islets and HIT-T15 B cells. / Noor H, Hammonds P, Sutton R, Ashcroft SJ. / Diabetologia. June 1989; 32(6): pp 354-359.
(15)
The Effect of Tinospora crispa on Serum Glucose and Insulin Levels in Patients with Type 2 Diabetes Mellitus
/ Theerawut Klangjareonchai and Chulaporn Roongpisuthipong / Journal of Biomedicine and Biotechnology, Volume 2012 / doi:10.1155/2012/808762
(16)
Inhibitory Properties of Tinospora crispa Extracts on TNF-α Induced Inflammation on Human Umbilical Vein Endothelial Cells (HUVECS) / Ihsan Safwan Kamarazaman, Zulkhairi Hj. Amom , Rasadah Mat Ali , Abdah Md Akim , Khairunnuur Fairuz Azman , Daryl Jesus Arapoc , Mohd Kamal Nik Hassan , Mohd Shahidan Mohd Arshad , Zamree Md Shah and Khairul Kamilah Abdul Kadir / International Journal of Tropical Medicine, 7: 24-29. / DOI: 10.3923/ijtmed.2012.24.29
(17)
Toxicological study of crude extract of Tinospora crispa Mier ex Hook F.& Thoms / Pranee Chavalittumrong, Aimmanus Attawish, Anchalee Chuthaputti, Pranee Chuntapet / Thai Journal of Pharmaceutical Sciences 1997; 21(4): pp 199-210
(18)
Antimicrobial, Cytotoxicity and Antioxidant Activity of Tinospora crispa / Haque Aminul Md., Islam Ashraful S. M. and Shahriar Mohammad / Journal of Pharmaceutical and Biomedical Sciences, 2011;13 (12)
(19)
Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice. / doi:10.1016/j.phymed.2012.03.009 / The Free Library by Farlex
(20)
AN AQUEOUS EXTRACT OF TINOSPORA CRISPA POSSESSES ANTIOXIDATIVE PROPERTIES AND REDUCES ATHEROSCLEROSIS IN HYPERCHOLESTEROLEMIC-INDUCED RABBITS / ZULKHAIRI AMOM*, KHAIRUNNUUR FAIRUZ AZMAN, NOR AMALINA ISMAIL, ZAMREE MD SHAH, MOHD SHAHIDAN MOHAMAD ARSHAD / Journal of Food Biochemistry, Volume 35, Issue 4, pages 1083–1098, August 2011 / DOI: 10.1111/j.1745-4514.2010.00436.x
(21)
Effect of Tinospora crispa on thioacetamide-induced liver cirrhosis in rats / Farkaad A Kadir, Faizah Othman, Mahmood Ameen Abdulla, Farida Hussan, Pouya Hassandarvish / Indian Journ of Pharmacology, 2011, Vol 43, No 1, pp 64-68 / DOI: 10.4103/0253-7613.75673
(22)
Anti-proliferative and antioxidant effects of Tinospora crispa (Batawali) / Ibahim MJ, Wan-Nor I'zzah WMZ, Narimah AHH, Nurul Asyikin Z, Siti-Nur Shafinas SAR, Froemming GA / Biomedical Research, 2011;
22 (1): pp 57-62
(23)
Study on cardiac contractility of cycloeucalenol and cycloeucalenone isolated from Tinospora crispa /
Kongkathip N, Dhumma-upakorn P, Kongkathip B, Chawananoraset K, Sangchomkaeo P, Hatthakitpanichakul S. / J Ethnopharmacol. 2002 Nov;83(1-2):95-9.
(24)
Tinospora crispa (L.) Hook. f. & Thomson / Synonyms / The Plant List
(25)
Antidiabetic Effect of Oral Borapetol B Compound, Isolated from the Plant Tinospora crispa, by Stimulating Insulin Release. / Lokman FE, Gu HF, Wan Mohamud WN, Yusoff MM, Chia KL, Ostenson CG. / Evid Based Complement Alternat Med. 2013;2013:727602 / doi: 10.1155/2013/727602. Epub 2013 Nov 10.
(26)
ANTIMALARIAL ACTIVITY OF STEM EXTRACT OF TINOSPORA CRISPA AGAINST PLASMODIUM BERGHEI INFECTION IN MICE / Jariya Niljan, Ubonwan Jaihan, Somdet Srichairatanakool, Chairat Uthaipibull, Voravuth Somsak / Journal of Health Research, Jan 2014; 28(3): pp 199-204. 
(27)
In vitro interaction of combined plants: Tinospora crispa and Swietenia mahagoni against Methicillin- resistant Staphylococcus aureus (MRSA)
/ N. T. Al- alusi*, F. A. Kadir, S. Ismail and M. A. Abdullah / African Journal of Microbiology Research Vol. 4(21), pp. 2309-2312, 4 November, 2010
(28)
Hypoglycemic Diterpenoids from Tinospora crispa / Sio-Hong Lam, Chi-Tun Ruan, Po-Hung Hsieh, Ming-Jai Su*, and Shoei-Sheng Lee* / J. Nat. Prod., 2012; 75(2): pp 153–159 / DOI: 10.1021/np200692v
(29
Immunomodulatory effect of an isolated fraction from Tinospora crispa on intracellular expression of INF-γ, IL-6 and IL-8 / Walaa Najm Abood, Iman Fahmi, Mahmood Ameen Abdulla* and Salmah Ismail / BMC Complementary and Alternative Medicine 2014, 14:205 / https://doi.org/10.1186/1472-6882-14-205
(30)
Effects of an n-butanol extract from the stem of Tinospora crispa on blood pressure and heart rate in anesthetized rats / Siwaporn Praman, Michael J. Mulvany, Yves Allenbach, Andrew Marston, Kurt Hostettmann, Poungpen Sirirugsa, Chaweewan Jansakul / Journal of Ethnopharmacology, 2011; 133: pp 675–686
(31)
ALPHA-GLUCOSIDASE INHIBITOR ACTIVITY AND CHARACTERIZATION OF ENDOPHYTIC ACTINOMYCETES ISOLATED FROM SOME INDONESIAN DIABETIC MEDICINAL PLANTS / Pujiyanto et al. / Int J Pharm Pharm Sci, Vol 4, Suppl 1, 327-333
(32)
Tinospora crispa extract inhibits MMP-13 and migration of head and neck squamous cell carcinoma cell lines / Hataipan Phienwej, Ih-si Swasdichira, Surattana Amnuoypol, Prasit Pavasant, Piyamas Sumrejkanchanakij / Asian Pac J Trop Biomed, 2015; 5(9): pp 738–743
(33)
ANTI-ATHEROGENIC AND ANTIOXIDANT ACTIVITIES OF PATAWALI (TINOSPORA CRISPA) ON RABBITS FED WITH HIGH CHOLESTEROL DIET / HASNAH BAHARI / Thesis, July 2007
(34)
Ethnomedicinal plants used by traditional healers in Phatthalung Province, Peninsular Thailand / Maneenoon et al. / Journal of Ethnobiology and Ethnomedicine (2015) 11:43 / DOI 10.1186/s13002-015-0031-5
(35)
Wound healing potential of Tinospora Crispa (Willd.) Miers [Menispermaceae] stem on diabetic mice / Ryan O Arcueno, Jinger Lyn B Retumban, Joycelyn E Echano, Jonathan Jaime G Guerrero / Journal of Medicinal Plants Studies, 2015; 3(2): pp 106-109
(36)
Protective Effects of Tinospora crispa Stem Extract on Renal Damage and Hemolysis during Plasmodium berghei Infection in Mice / Narain Nutham, Sakuna Sakulmettatham, Suwit Klongthalay, Palatip Chutoam, and Voravuth Somsak / J Pathog. 2015; 2015: 738608 / doi: 10.1155/2015/738608
(37)
Biological Properties of Tinospora crispa (Akar Patawali) and Its Antiproliferative Activities on Selected Human Cancer Cell Lines / Zulkhairi A, Abdah MA, M Kamal NH, Nursakinah I, Moklas MAM, Hasnah B, Fazali F, Khairunnur FA, Kamilah KAK, Zamree MS & Shahidan MMA / Mal J Nutr 14(2): 173 - 187, 2008
(38)
Randomized Controlled Trial of Tinospora crispa for Additional Therapy in Patients with Type 2 Diabetes Mellitus / Chawanya Sangsuwan MD*, Suthipol Udompanthurak MSc**, Sathit Vannasaeng MD*, Visanu Thamlikitkul MD* / J Med Assoc Thai 2004; 87(5): 543-6
(39)
Antimicrobial Activity of Tinospora crispa Root Extracts / Asif Iqbal Chittur Mohammed, Gunjan Manish, Chellappan Kumar Dinesh / IJRAP, May-June 2012; 3(3),
(40)
Antioxidant Activity of Methanol Extract of Tinospora crispa and Tabernaemontana corymbosa / Heida Nadia Zulkefli, JamaudiN Mohammad* & Nurhayati Zainal Abidin / Sains Malaysiana, 2013; 42(6): pp 697–706
(42)
Review of Anti-Hyperglycemic Effect of Tinospora crispa / Theerawut KLANGJAREONCHAI, Supanee PUTADECHAKUM, Chulaporn ROONGPISUTHIPONG / Walailak Journal of Science and Technology, 2015; Vol 12, No 5
(43)
Effect of Aqueous Crude Extract of Tinospora Crispa on Plasmodium Berghei Induced Liver Damage in Mice / Voravuth Somsak*, Jutatip Kittitorn, Sukanya Chachiyo, Somdet Srichairatanakool and Chairat Uthaipibull / Malar Chemoth Cont Elimination 4:127. / doi: 10.4172/2470-6965.1000127
(44)
In vitro interaction of combined plants: Tinospora crispa and Swietenia mahagoni against Methicillin- resistant Staphylococcus aureus (MRSA) / N. T. Al- alusi*, F. A. Kadir, S. Ismail and M. A. Abdullah / African Journal of Microbiology Research Vol. 4(21), pp. 2309-2312, 4 November, 2010
(45)
IN VIVO ANTIPARASITIC ACTIVITY OF THE THAI TRADITIONAL MEDICINE PLANT-TINOSPORA CRISPA-AGAINST PLASMODIUM YOELII / Thanaporn Rungruang and Thidarut Boonmars / SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH, Vol 40 No. 5 September 2009
(46)
The Activation of GLUT1, AMPK alpha and PPAR gamma by Tinospora crispa in L6 Myotubes
/ Kusumarn Noipha, Putrada Ninla-aesong / Spatula DD. 2011; 1(4): pp 245-249 / doi: 10.5455/spatula.20111206115628
(47)
Immunostimulatory effects of the standardized extract of Tinospora crispa on innate immune responses in Wistar Kyoto rats / Ahmad W, Jantan I, Kumolosasi E, Abbas Bukhari SN / Drug Design, Development and Therapy, Volume 9 / DOI https://doi.org/10.2147/DDDT.S85405 / Standardized extract of Tinospora crispastimulates innate and adaptive immune responses in Balb/c mice / Food & Function. 2-16, Issue 3
(48)
Assessment of In-vitro Wound Healing Activity of the Tinospora crispa Extracts / Santalaxme Vijendren, Shankar Jothi, Kushha Rajandran, Vignesh Muruganandham / International Journal of Pharmacology and Pharmaceutical Technology (IJPPT), 2017; Vol1, Issue 2
(49)
Screening of Volatile Compounds of Brotowali (Tinospora Crispa) and Antifungal Activity Against Candida albicans / Warsinah, Harwoko, Nuryanti / International Journal of Pharmacognosy and Phytochemical Research 2015; 7(1); 132-136
(50)
Insulin Sensitivity Enhancement of the Mixture of Tinospora Crispa and Gelam (Melaleuca Cajuputi) Honey and Its Antiproliferative Activity on Hepatocellular carcinoma, HepG2: A Preliminary Study
/ Mohd Nazri Abu, Muhammad Ashraf Mohd Salleh, Nabilatul Hani Mohd Radzman, Wan Iryani Wan Ismail*, Rosmadi Mohd Yusoff, Hamzah Fansuri Hasan / Journal of Medical Research and Development (JMRD) Jul. 2013, Vol. 2 Iss. 3, PP. 48-54
(51)
EVALUATION OF THROMBOLYTIC ACTIVITY AND BRINE SHRIMP LETHALITY BIOASSAY OF METHANOL EXTRACT OF STEMS OF TINOSPORA CRISPA / Md. Ariful Islam, Zobaer A. Mahmud*, S.M. Abdur Rahman, Md. Monirujjaman and Sajal K. Saha / INTERNATIONAL JOURNAL OF
PHARMACEUTICAL SCIENCES AND RESEARCH (IJPSR),  2013; 4(3); pp 1148-1153
(52)
Antinociceptive and Anti-inflammatory Activities of Tinospora crispa in Various Animal Models / M.R. Sulaiman , Z.A. Zakaria and R. Lihan / International Journal of Tropical Medicine, 2008; 3: pp 66-69
(53)
HYPOGLYCEMIC EFFECT OF TINOSPORA CRISPA DRY POWDER IN OUTPATIENTS WITH METABOLIC SYNDROME AT KING CHULALONGKORN MEMORIAL HOSPITAL / Chutima Sriyapa,∗ Rawadee Dhumma-upakorn, Somkiat Sangwatanaroj, Ngampong Kongkathip and Sarinee Krittiyanunt / J Health Res 2009, 23(3): 125-133
(54)
Antiplasmodial Test of Tinospora crispa Stem Extract against Plasmodium falciparum 3D7 Strain In Vitro / Ihwan, Muhaimin Rifa, Fitri LE / Jurnal Kedokteran Brawijaya, Vol. 28, No. 2, Agustus 2014
(55)
The Significance of Tinospora crispa in Treatment of Diabetes Mellitus. / Thomas A, Rajesh EK, Kumar DS / Phytother Res.,  2016 Mar; 30(3): pp 357-66 / doi: 10.1002/ptr.5559
(56)
ANTI-INFLAMMATORY ACTIVITIES OF THE AQUEOUS EXTRACT OF THE STEM OF Tinospora crispa (FAMILY MENISPERMACEAE) / Regina Lourdes B.Hipol*, Maria Faye Nenette, M. Cariaga and Roland M. Hipol / Journal of Nature Studies 11 (1&2): 88-95
(57)
BIOACTIVITIES of ETRACTS from Tinospora crispa STEMS, Annona squamosa LEAVES, Musa sapientum FLOWERS, and Piper sarmentosum LEAVES in DIABETIC RATS / ChusriTalubmook and Nopparat Buddhakala / International Journal of Advancements in Research & Technology, Volume 2, Issue 6, June-2013
(58)
Effect of Tinospora crispa on glucose uptake in skeletal muscle: role of glucose transporter 1 expression and extracellular signal-regulated kinase1/2 activation / Kusumarn Noipha, Suvina Ratanachaiyavong, Juntipa Purintrapiban, Angkana Herunsalee, Putrada Ninla-aesong / Asian Biomedicine, June 2011; Vol 5, Issue 3 / DOIhttps://doi.org/10.5372/1905-7415.0503.047
(59)
Toxic hepatitis induced by a herbal medicine: Tinospora crispa. / The Free Library
(60)
Screening of Volatile Compounds of Brotowali (Tinospora Crispa) and Antifungal Activity Against Candida albicans / Warsinah, Harwoko, Nuryanti / International Journal of Pharmacognosy and Phytochemical Research 2015; 7(1); 132-136
(61)
Alkaloids content, cytotoxicity and anti-Toxoplasma gondii activity of Psidium guajava L. and Tinospora crispa / Wei Cai Lee, Roziahanim Mahmud, Rahmah Noordin, Suthagar Pillai Piaru, Shanmugapriya Perumal, Sabariah Ismail / Bangladesh Journal of Pharmacology, Nov 2012; Vol 7, No 4: pp 272-276 / doi:10.3329/bjp.v7i4.12499.
(62)
Cytotoxic Activity Assay of Tinocrisposide from Tinospora crispa on Human Cancer Cells / Adek Zamrud Adnan, Muhammad Taher, Tika Afriani, Dewi Imelda Roesma and Andani Eka Putra / Der Pharmacia Lettre, 2016, 8 (18):102-106
(63)
Artesunate-tinospora combination treatment decreases nuclear factor kappa-B and intercellular adhesion molecule-1 expression in mouse malarial models / Nur Izzati, Loeki Enggar Fitri, and Mochammad Dalhar / UNIVERSA MEDICINA, Sept-Dec 2016; Vol 35, No 3 /
DOI: http://dx.doi.org/10.18051/UnivMed.2016.v35.222-228
(64)
Safety, Efficacy, and Physicochemical Characterization of Tinospora crispaOintment: A Community-Based Formulation against Pediculus humanus capitis / Gerwin Louis Tapan Dela Torre, Kerstin Mariae Gonzales Ponsaran, Angelica Louise Dela Peña de Guzman, Richelle Ann Mallapre Manalo, Erna Custodio Arollado * / The Korean Journal of Parasitology 2017; 55(4): 409-416. / DOI: https://doi.org/10.3347/kjp.2017.55.4.409
(65)
A SHORT REVIEW ON POTENTIAL MALAY MEDICINE IN CONTROLLING OBESITY AND TREATING CANCERS / MUHAMMAD AMEERUL AMIN BAKAR, OMAR AND WAN IRYANI WAN ISMAIL / Journal of Sustainability Science and Management, June 2017; Volume 12, Number 1: pp 96-101
(66)
Crispene A, B, C and D, four new clerodane type furanoid diterpenes from Tinospora crispa (L.). /
Hossen F, Ahasan R, Haque MR, Begum B, Hasan CM. / Phcog Mag, 2016; Vol 12, Issue 45; pp 37-41 / DOI: 10.4103/0973-1296.176116
(67)
Determination of N-trans-feruloyltyramine content and nitric oxide inhibitory and antioxidant activities of Tinospora crispa / Attawadee SaeYoon*, Bhudsaban Sukkarn, Wichit Nosoongnoen, Chutima Jantarat, Poonsit Hiransai, Pajaree Sakdiset, Jiraporn Chingunpitak, Sunita Makchuchit, Arunporn Itharat / Asian Journal of Pharmaceutical Sciences (2015)
(68)
Effects of Tinospora crispa aqueous extract in regulating cholesterol metabolism in human hepatoma cancer cell line (Hep G2) / Zameree Md Shah, Mohd Kamal Nik Hasan, Shahidan Mohd Arshad, Khairul Kamilah Abdul Kadir, Ihsan Safwan Kamarazaman, Zulkhairi Amom, Rasadah Mat Ali, Daryl Jesus Arapoc / Journal of Medicinal Plants Research, November 2017; Vol 11, No 43: pp 673-682 / https://doi.org/10.5897/JMPR2017.6390
(69)
HERB - DRUG INTERACTION: THE EFFECT OF TINOSPORA CRISPA MIERS. ON DRUG METABOLISM IN RAT LIVER / Tan Phaik Tin / Thesis: Jan 2009 /
(70)
Toxic hepatitis induced by a herbal medicine: Tinospora crispa / Langrand J, Regnault H, Cachet X, Boudzidi C, Villa A F, Serfaty L, Garnier R, Michel S / Phytomedicine, 2014; Vol 21: pp 1120-1123
(71)
The anti proliferative roperties of tinospora crispa on triple negative breast cancer cell lines
/ Reyadh Radhi Al-Rashidi / Universiti Teknologi Mara: Institutional Repository
(72)
Larvicidal Activity of Tinospora crispa (Menispermaceae) Fruit Extract Against Filarial Vector Culex quinquefasciatus / Jibon Kumar Pal, Aniket Singh, Anjali Rawani, Goutam Chandra / Journal of Mosquito Research, 2016; Vol 6, No 35 / doi: 10.5376/jmr.2016.06.0035
(73)
Tinospora crispa (L.) Hook. f. & Thomson: A Review of Its Ethnobotanical, Phytochemical, and Pharmacological Aspects / Wagas Ahmad, Ibrahim Jantan and Syed N A Bukhari / Front Pharmacol/ 2016; 7: 59 / doi: 10.3389/fphar.2016.00059 / PMCID: PMC4800188 / PMID: 27047378
(74)
EFFECT OF ETHANOLIC EXTRACT OF TINOSPORA CRISPA L FROM INDONESIA IN ALLOXAN INDUCED LIVER DAMAGE / EM SUTRISNA, FAHRIZAL ARIA SAHADEWA, IKBAR ARDIANSYAH / Int J Pharm Pharm Sci., Vol 9, Issue 8: pp 65-68
(75)
Tinospora crispa medicine composition with effect of blood sugar reduction and preparation method thereof  / CN104138417A China
(76)
Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa / Xavier Cachet, Jerome Langrand, Ludivine Riffault-Valois, Chouaha Bouizidi, Cyril Colas, Annabelle Dugay, Sylvie Michel, & Denis Boucaud-Maitre / Scientific Reports, 2018;  8, Article number: 13520 / Scientific Reports,  2018; 8, Article number: 13520
(77)
Anti-hyperglycemic activity of a tablet from Tinospora crispa (Linne) Miers Ex Hooks F & Thomson (Family Menispermaceae) / Paguirigan RE, Roxas ICP, Go JMDG / Thesis, 2007
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HERB-DRUG INTERACTION: THE EFFECT OF TINOSPORA CR/SPA MIERS. ON DRUG METABOLISM IN RAT LIVER / Tan Phaik Tin / Thesis, Jan 2009
(79)
ANTIBACTERTIAL PROPERTY AND TOXCITY STUDY OF MEDICINAL PLANT TINOSPORA CRISPA L.
/ Altamar Khadijah Ahmedy / Dissertation: Master of Biotechnology / Faculty of Science, University of Malaya, Kuala Lumpur, 2010
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BIOACTIVITIES of ETRACTS from Tinospora crispa STEMS, Annona squamosa LEAVES, Musa sapientum FLOWERS, and Piper sarmentosum LEAVES in DIABETIC RATS / Chusri Talubmook and Nopparat Buddhakala / International Journal of Advancements in Research & Technology, June 2013, Volume 2, Issue 6: pp 144-149
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Sensitivity test of Escherichia coli againts extract of Tinospora crispa / Lucia Muslimin, Nurul Rezqi Hazrah, Abdul Wahid Jamaluddin / Proceedings of the 1st International Conference in One Health (ICOH 2017) / DOI: https://doi.org/10.2991/icoh-17.2018.21
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Effect of water extract of Tinospora crispa (L.) Hook. F. & Thomson on two breast cancer cell lines MCF-7 and MDA-MB-231  / Ibahim M. J.Wan-Nor I'zzah W. M. Z.Froemming G. A. R. / AGRIS: INTERNATIONAL INFORMATION SYSTEM FOR THE AGRICULTURAL SCIENCE AND TECHNOLOGY
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EVALUATION OF ANALGESIC AND ANTIMICROBIAL ACTIVITY OF DIFFERENT FRACTIONS OF CRUDE METHANOL EXTRACT OF TINOSPORA CRISPA STEM. / Md. Ariful Islam, Mohammad Ruhul Amin, Zobaer Al Mahmud / International Journal of Pharma Sciences and Research (IJPSR), Jan 2014; 5(1): pp 16-21
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Mechanism of apoptosis induced in hepatoma G2 (HepG2) cell lines by Tinospora crispa: targeting signalling of the insulin-like growth factor (IGF) system and the insulin signalling (IS) pathway / Mohd Nazri Abu, Wan Iryani Wan Ismail, Wan Shahriman Yushdie Wan Yusoff et al / Asian Pacific Journal of Tropical Disease, June 2014; 4(3) / https://doi.org/10.1016/S2222-1808(14)60539-9
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Study on cardiac contractility of cycloeucalenol and cycloeucalenone isolated from Tinospora crispa
/ / Journal of Ethnopharmacology, 2002; 83(1/2): pp 95-99 / PMID: 12413712
/ DOI: 10.1016/s0378-8741(02)00210-6
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Phyto chemical and bio activities research on Tinospora crispa (Patawali) / Shakirah Abdul Shukor / Research and Development Seminar 2010; Bangi (Malaysia); 12-15 Oct 2010.
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Lipid lowering and anti-atherosclerotic properties of Tinospora crispa aqueous extract on high-cholesterol diet-induced hyperlipidemic rabbits / Zamree, M. S., Ihsan Safwan, K., Khairul Kamilah A. K., Mohd Kamal N. H., Rasadah, M. A., Mohd Shahidan M. A., Daryl, J. A. and Zulkhairi, A. / African Journal of Biotechnology, 26 Aug 2015; 14(34): pp 2604-2610 / DOI: 10.5897/AJB2015.14787


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