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Coscinium fenestratum (Gartn.) Colebr.

Synonyms

Coscinium walliichianum Miers, Coscinium blumeanum (non Miers ex Hook.f. et Thomson) Miq.

Vernacular Names:

 Malaysia: Mengkunyit, Sekunyit, Kekunyit, Badi
 English: False Calumba, Ceylon Calumba Root, Turmeric Tree

General Information

Description

This woody climber is found in Southeast Asia and Peninsular Malaysia.[1]

Plant Part Used

Wood, stem, root.[1]

Chemical Constituents

A minor alkaloid, 12,13-dihydro-8-oxo-berberine [5,6,13,13a-tetrahydo-9,10-dimethoxydibenzo(a,g)1,3-dibenzodioxolo(5,6a)quinalizine-8-one], as well as berberine, oxyberberine, tetrahydroberberine (canadine), sitosterol and stigmasterol were isolated from Coscinium fenestratum.[2] Rojsanga et al. had developed an optimal extraction procedure for the determination of berberine from alkaloid extracts of dried stems using 80% ethanol. The recovery of berberine was about 98% when detected and quantified by TLC-densitometric method.[3]

Traditional Use:

An infusion of the woody part is administered as a substitution for calumba root to reduce fever. It is also useful as a stomachic.[1] 

In traditional medicine, the stem and roots are claimed to have been used as an antibacterial and an antipyretic. They are useful to treat dysentery, malaria, fever and ophthalmia.[1]

Pre-Clinical Data

Pharmacology

Hypotensive activity

A 50% ethanol extract of Coscinium fenestratum stem extract was investigated for its hypotensive action in several anaesthesised animal models. The plant extract which was found to reduce the blood pressure of these animals however, was not modified by alpha and beta adregenic blockers, cholinergic and histaminergic antagonists or by ganglion blocking agents. The hypotensive effect was more prominent in spinal-transected animals. The ethanol extract of the stem of Coscinium fenestratum inhibited the presser responses to epinephrine, norepinephrine, the nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP) and depressor responses to acetylcholine and histamine. The ethanol extract failed to demonstrate any hypotension when administered via cannula into the lateral cerebral ventricle. The extract also did not exhibit grossly observable central nervous effects up to doses of 800mg/kg (p.o). The oral LD50 was estimated to be 1200mg/kg in mice.[4] 

In another study, the water extract from the dried stem of Coscinium fenestratum was assessed for hypotensive and vasorelaxant effects. The extract was obtained by boiling the dried stem of Coscinium fenestratum in water, concentrated and freeze-dried until a yellowish-brown dried powder was obtained. Freshly prepared solutions from the dried powder were prepared for use in the experiments with an animal model. The study demonstrated that the water extract was effective in reducing blood pressure in anaesthetised normotensive rats in a dose-related manner with rapid onset and short duration. This supports the previous study by Singh et al. The water extract showed endothelium-dependent and independent vasorelaxant activity in isolated rat aortic rings precontracted with phenylephrine (1mM) and KCl (60mM). The vasorelaxant effect was reduced by L-N(ω)-nitro-arginine methyl ester (L-NAME) (100mM), an inhibitor of nitric oxide synthase indicating some role of endothelium derived relaxing factors such as nitric oxide.[5]

Antioxidant activity

A study to assess the antioxidant effect of methanol extract from the stem of Coscinium fenestratum was performed on carbon tetrachloride-intoxicated rat liver. The methanol extract was given orally to the hepatotoxic rats at a dose of 60mg/kg body weight every day for 90 days. Lipid peroxidation in hepatotoxic rats was shown by a marked increase in the levels of thiobarbituric acid reactive substances and diene conjugates. A profound reduction in glutathione content in the liver and the decreased activities of antioxidant enzymes support the finding. On the other hand, hepatotoxic rats treated with the methanol extract retained an almost normal level of these constituents. The results demonstrated that the methanol extract from Coscinium fenestratum was effective in fighting oxidative stress due to hepatic damage.[6] 

Another study to assess the antioxidant activity of the alcoholic stem extract of Coscinium fenestratum was investigated in streptozotocin-nicotinamide induced type 2 diabetic rats. Diabetic rats administered with alcoholic extract of Coscinium fenestratum showed significant increase in the activity of enzymatic antioxidants, such as catalase, glutathione peroxidase, glutathione synthetase, peroxidase and superoxide dismutase and in the nonenzymatic oxidants ascorbic acid, ceruloplasmin and tocopherol. The antioxidant activity of Coscinium fenestratum could be due to the presence of berberine and phenolic compounds.[7]

Antiplasmodial activity

In a study on Vietnamese traditional medicinal plants, 42 extracts (MeOH, MeOH-H2O, and H2O for each plant) prepared from 14 medicinal plants which were used for the treatment of malaria traditionally were investigated for in vitro antimalarial effect against the growth of the chloroquine-resistant Plasmodium falciparum strain FCR-3 and their toxicity against mouse mammary FM3A cells which served as a model host. Amongst the 14 medicinal plants, 24 extracts were found to be active against P. falciparum and the three extracts of Coscinium fenestratum possessed strong activity, in which the MeOH extract was the strongest (EC50, 0.5mg/ml) among all 24 active extracts. In vitro experiment demonstrated that they all possessed strong antiplasmodial activity with EC50 values of 1.3, 1.9 and 2.8mM, respectively.[8]

Antihepatotoxic activity

Antihepatotoxic activity of methanol extract of Coscinium fenestratum was investigated against carbon tetrachloride-induced hepatopathy in rats. The hepatotoxic rats were treated orally by intubation with the methanol extract at a dose of 60mg/kg body weight every day for 90 days. The activity of serum marker enzymes such as AST, ALT, ALP, GGT, LDH, G-6-PD in liver were studied for their hepatotoxic effect. Other biochemical parameters studied were total protein, total lipids, triglycerides, phospholipids and cholesterol in serum, liver and kidney. The activities of all the marker enzymes showed a significant elevation in the hepatotoxic rats, however the levels were significantly recovered towards almost normal levels in hepatotoxic rats treated with the methanol extract of the plant.[9]

Antidiabetic activity

The study by Punitha et al. also investigated the antidiabetic activity of Coscinium fenestratum in a rat model of type 2 diabetes mellitus. In this study, a group of diabetic-induced animals was administered orally with Coscinium fenestratum alcoholic extract 250mg/kg body weight and another group was administered with Coscinium fenestratum alcoholic extract 500mg/kg body weight. The enzymes involved in the carbohydrate metabolism evaluated included hexokinase, glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH), glucose-6-phosphatase (G6P) and alanine amino-transferase (ALT). Urea and creatinine levels were also estimated in these rats. The results showed that the diabetic rats treated with 500mg/kg of the alcoholic extract of Coscinium fenestratum exhibited better enzyme activity than those treated with 250mg/kg dose of the alcoholic extract. Effects of alcoholic extract on glycolytic enzymes (hexokinase, G6PD, LDH) demonstrated a significant increase in their levels. On the other hand, the treated diabetic rats exhibited a significant decrease in the levels of G6P and ALT, indicating the possibility of the suppression of hepatic gluconeogenesis and glucose output from the liver. Serum urea and creatinine levels were also decreased significantly with the diabetic control. This investigation demonstrates significant antidiabetic activity of Coscinium fenestratum.[6]

The antidiabetic activity of alcoholic stem extract of Coscinium fenestratum was further investigated in streptozotocin (STZ)-nicotinamide induced type 2 diabetic rats. In this study, the oral glucose tolerance test and normoglycaemic studies revealed that the alcoholic extract of the stem had the capacity to lower blood glucose levels. This study suggested that the hypoglycaemic activity of Coscinium fenestratum did not stimulate the secretion of insulin in animals treated with the plant extract. The post-prandial glucose reduction was not caused by any extra load on the pancreatic b cells and/or stimulation of glucose uptake by peripheral tissues. In addition, the Coscinium fenestratum alcoholic extract treated rats showed a weight loss which may be due directly to the lipid lowering activity of the extract or indirectly to the influence of various lipid regulation systems. Berberine is thought to be the contributing constituent in the significant antidiabetic activity of the alcoholic extract of Coscinium fenestratum.[10][11]

Antibacterial activity

Antibacterial activities of Coscinium fenestratum methanol extract, water extract and berberine were investigated by using filter paper disc diffusion method against various microorganisms. Both methanol and water extracts tested positive for berberine by HPLC method. The result of this study showed that the active principle berberine was found to be active against the microorganisms tested. The activity of methanol extract and water extract was as good as the activity of berberine against Klebsiella pneumoniae only. However, the activity of methanol extract and water extract against other microorganisms was low compared to the activity of berberine which led to the conclusion that the antibacterial activity of Coscinium fenestratum is mainly controlled by its active alkaloid berberine.[12] 

Antiproliferative activity

In search of more effective anticancer drugs with high selectivity against only malignant cells and with the ability to repress tumour metastasis, various Vietnamese medicinal plants which have been used as tonics, for treatment of inflammation, cancer and other conditions were collected. Methanol, methanol-water (1:1) and water extracts were prepared and their antiproliferative activities examined against highly metastatic human HT-1080 fibrosarcoma cells, human cervix HeLa adenocarcinoma, human lung A549 adenocarcinoma, murine colon 26-L5 carcinoma, murine Lewis lung carcinoma (LLC) and murine B16-BL6 melanoma cells. Among them, methanol extract of Coscinium fenestratum exhibited antiproliferative activity against highly metastatic human HT-1080 fibrosarcoma cells in a concentration-dependent manner with EC50 value of 11.7mg/ml. The methanol and methanol-water extracts of Coscinium fenestratum showed strong and selective antiproliferative activities against two kinds of lung carcinoma cells, A549 and LLC; methanol extract: EC50 against LLC cells, 1.65mg/ml; methanol-water extract: EC50 against A549 and LLC cells, 2.88 and 2.84mg/ml, respectively. It is interesting to note that the principle constituent of Coscinium fenestratum, berberine was earlier reported to inhibit metastasis of LLC cells. The methanol and methanol-water extracts also showed antiproliferative activities against B16-BL6 cells.[13]

Toxicities

Neurotoxicity activity

A study to observe the effect of Coscinium fenestratum stem on neurotoxicity and neurobehaviour was carried out in various brain areas of an animal model. The alcoholic extract of the Coscinium fenestratum stem was administered orally to rats at dosages of 5, 10 and 20mg/kg body weight, once daily for 14 days. The extracts significantly increased the body weight of rats and induced neurotoxicity in the cerebral cortex, hippocampus and striatum. However, the extracts were found to produce no acute toxicity in the experimental rats except increased licking behaviour. The plant extract did not show any anxiolytic activity, antidepression, sensory motor co-ordination impairment and ataxia. The study concluded that the application of long-term use Coscinium fenestratum products as drugs, supplementary foods or for various medicinal purposes should be reconsidered, and humans should be very careful in order to avoid its toxicity.[14]

Subchronic and acute toxicity tests

The subchronic and acute toxicity tests were performed in rats to establish the safety of the water extract of the stem of Coscinium fenestratum. The water extract was fairly non-toxic since the single dose of 5000mg/kg body weight did not cause death, or any toxic signs and symptoms. In subchronic toxicity study, the repeated dose of plant extract did not cause changes of rat behaviour or motor activity. No noticeable changes in body weight and food intake were observed demonstrating that the plant water extract at the dose of 2500mg/kg body weight did not significantly change the appetite or metabolism of treated animals. These finding were different from the previous study by Wattanathorn et al. [13] which used alcoholic extract of the plant. The different findings indicate that the compounds which produced neurotoxicity were not extracted with water. Due to this statistical difference, further studies should be done to confirm the safety of this plant when it is used over a long period of time.[5]

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

No documentation

Use in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation

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  1) Botanical Info

References

  1. Herbal Medicine Research Centre, Institute for Medical Research, Kuala Lumpur. Compendium of Medicinal Plants Used in Malaysia. 2002; 1:219.
  2. Malhotra,S., Taneja, S.C. & Dhar, K.L. Minor alkaloid from Coscinium fenestratum.Phytochemistry. 1989; 28(7):1998-9. Abstract
  3. Rojsanga, P., Gritsanapan, W. & Suntornsuk, L. Determination of berberine content in the stems extracts of Coscinium fenestratum by TLC densitometry. Med. Princ. Pract. 2006; 15 (5): 373-8. Abstract.
  4. Singh, G.B. et al. Hypotensive action of a Coscinium fenestratum stem extract. J. Ethnopharmacol. 1990; 30: 151-5. Abstract
  5. Wongcome, T. et al. Hypotensive effect and toxicology of the extract from Coscinium fenestratum (Gaertn.) Colebr. J. Ethnopharmacol. 2007; 111:468-75.
  6. Venukumar, M.R. & Latha, M.S. Antioxidant effect of Coscinium fenestratum in carbon tetrachloride treated rats. Indian J. Physiol. Pharmacol. 2002; 46: 223-8. Abstract
  7. Punitha, I.S.R. et al. Alcoholic Stem Extract of Coscinium fenestratum regulates carbohydrate metabolism and improves antioxidant status in streptozotocin-nicotinamide induced diabetic rats. Evid Based Complement Alternat Med. 2005; 2:(3): 375–81.
  8. Quan Le Tran, et al. In vitro antiplasmodial activity of antimalarial medicinal plants used in Vietnamese traditional medicine. J. Ethnopharmacol. 2003; 86: 249-52.
  9. Venukumar, M.R. & Latha,M.S. Effect of Coscinium fenestratum on hepatotoxicity in rats. Indian J. Exp. Biol. 2004; 42: 792-7. Abstract
  10. Shirwaikar, A., Rajendran, K. & Punitha, I.S.R. Antidiabetic activity of alcoholic stem extract of Coscinium fenestratum in streptozotocin-nicotinamide induced type 2 diabetic rats. J. Ethnopharmacol. 2005; 97:369-74.
  11. Shirwaikar, A., Rajendran, K. & Punitha, I.S.R. Antihyperglycaemic activity of the aqueous stem extract of Coscinium fenestratum in non-insulin dependent diabetic rats. Pharmacol. Biol. 2005; 43: 707-12.
  12. Nair, G.M., Narasimhan, S., Shuburaj, S. & Abraham, T.K. Antibacterial effects of Coscinium fenestratum. Fitoterapia. 2005; 76: 585-7.
  13. Ueda, J. et al. Antiproliferative activity of Vietnamese medicinal plants. Biol. Pharm. Bull. 2002; 25: 753-60.
  14. Wattanathorn, J. et al. Neurotoxicity of Coscinium fenestratum stem, a medicinal plant used in traditional medicine. Food and Chem. Toxicol. 2006; 44: 1327-33.

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