Long-Term Effects of Kratom (Mitragyna speciosa) Use

@#Introduction: Kratom or (Mitragyna speciosa) leaves are consumed as a folk remedy and opioid substitute in the Southeast Asian region. There is still a lack of information about the long-term or toxic-causing effects of kratom use. Methods: A total of thirteen regular kratom users, with long-term (>20 twenty years) kratom use history were recruited for this cross-sectional pilot study. Respondents were required to undergo a blood-test and laboratory anaysis was conducted to determine the mitragynine content in an acquired street sample of kratom. Results: The regular, longterm consumption of brewed kratom decoction did not cause any significant alterations in haematological, kidney, liver, thyroid, inflammatory and gastrointestinal analytes in a cohort of kratom users who had no history of substance misuse. However, those who had a higher intake (>3 glasses per day) of kratom exhibited higher lipid values (except for HDL-cholesterol), and a moderate elevation of homocysteine level. Conclusion: Long-term (>20 years with a daily intake of ≥87.54mg of mitragynine) kratom consumption was not associated with altered biochemical levels, although prolonged and heavy use (>3 glasses daily) may result in cardiovascular risks. The latter finding, however, requires further investigation.

Garcinexanthone G, a Selective Butyrylcholinesterase Inhibitor from the Stem Bark of Garcinia atroviridis

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ± 1.57 µg/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ± 2.41 µg/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.

Influence of Extracting Solvent on Pharmacological Activity and Cytotoxicity of Polygonum minus, a Commonly Consumed Herb in Southeast Asia.

OBJECTIVE: To investigate the antihyperlipidemic, antioxidant, and cytotoxic effect of aqueous and methanol extract of leaves of Polygonum minus. MATERIALS AND METHODS: Acute antihyperlipidemic effect was studied on chemically induced hyperlipidemic rat model. Treated groups received aqueous and methanol extract of leaves of P. minus respectively (1000 mg/kg; oral) whereas standard treated group received atorvastatin (60 mg/kg; oral) for 3 consecutive days. Blood samples were collected at fixed intervals for lipid profile analysis. Antioxidant effects were studied using 1,1-diphenyl-2-picrylhydrazyl, 2,2-azinobis 3-ethylbenzothiazoline 6-sulfonate, and ferric reducing antioxidant power assays. The total flavonoids content and total phenolic contents were also estimated. Cytotoxicity of both extracts was studied on one normal and three cancer cell lines using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay method. RESULTS: The methanol extract showed significant reduction in total cholesterol (P < 0.001), triglycerides (P < 0.01), LDL (P < 0.05), VLDL (P < 0.01), atherogenic index (P < 0.001), and elevation of HDL (P < 0.05) levels than the aqueous extract. Similarly, the antioxidant investigations also demonstrated that the methanol extract had higher antioxidant capacity than aqueous extract. Both extracts were not toxic to normal (EA.hy926) as well as to cancer (HCT116, HT29, and HeLa) cells. Significant correlation was demonstrated between total phenolic and total flavonoids contents with the antioxidant activity but not with the antihyperlipidemic effect, suggesting other groups of chemical constituents may be mainly responsible for the antihyperlipidemic effect of this plant. CONCLUSION: The study demonstrated that the presence and extent of bioactivities are influenced by solvents used for extraction. This study confirmed the antihyperlipidemic effect of leaves of P. minus in acute hyperlipidemic rat model. SUMMARY: Polygonum minus is an herbaceous flowering plant.This plant possess high amount of phenolics and flavonoidsThis study focused on the antioxidant, cytotoxicity and antihyperlipidemic effect of aqueous and methanol extracts of leaves of P. minusThe extracts possess significant antioxidant activity and antihyperlipidemic activity but they are not toxic to normal and cancer cells tested.The antioxidant activity is well correlated with phenolic and flavonoids contents but the antihyperlipidemic activity is not correlated with antioxidant effect. Abbreviations used: CVDs: Cardiovascular diseases, LDL: Low-density lipoprotein, DDPH: 1,1-Diphenyl-2-picrylhydrazyl radical, TPTZ: 2,4,6,-tris(1-pyridyl)-5-triazine, ABTS: 2,2'-Azino-di-[3-ethylbenzthiazoline Sulfonate], HDL: High-density lipoprotein, VLDL: Very low-density lipoprotein, TC: Total cholesterol, TG: Triglycerides, EC50: Half maximal effective concentration, LD50: Median lethal dose.

Evaluation of methanol extract of Polygonum minus Huds. leaves for its hepatoprotective activity

Aims: Hepatotoxicity is a serious health risk and treatment options are inadequate. Polygonum minus Huds. (Family: Polygonaceae) is an antioxidant rich, commonly available plant in Malaysia and used in the Malay folk medicine. The leaves are also considered as one of the salad plants and flavouring agent for food delicacies. The present study evaluates the hepatoprotective activity of methanol extract of P. minus leaves on carbon tetrachloride (CCl4) and paracetamol-induced hepatotoxicity in Sprague Dawley rats. Methodology and results: Methanol extract of P. minus (MEPM) was prepared by maceration method. The standard drug and MEPM treated groups of rats were administered with silymarin (50 mg/kg) or MEPM (200 mg/kg or 400 mg/kg), respectively for 14 days in both experimental models. All the animals in the CCl4-induced model were administered CCl4 and paracetamol in the other model except to respective normal control group to induce liver toxicity. Estimation of body weight and liver weight, biochemical parameters including total protein, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin levels and histopathological studies were conducted. The MEPM was found to have significant hepatoprotective activity in rats with CCl4 and paracetamol-induced liver damage as noted from the analysis of body weight, serum marker enzyme activity and histopathology. Conclusion, significance and impact study: The MEPM possesses significant hepatoprotective activity while the activity is increased with dose in both experimental models. Inclusion of P. minus leaves in the food may be recommended as it may help to counteract different types of chemical-induced liver damage.

Hypoglycemic and anti-hyperglycemic study of Ocimum tenuiflorum L. leaves extract in normal and streptozotocin-induced diabetic rats

Objective To investigate the antidiabetic activity of Ocimum tenuiflorum L. (O. tenuiflorum) leaves used in the traditional medicine management of diabetes in Malaysia. Methods O. tenuiflorum leaves were extracted sequentially with hexane, chloroform, ethyl acetate, methanol, and water. The extracts were evaluated in terms of antidiabetic activity by using acute, subcutaneous glucose tolerance, and sub-chronic tests in streptozotocin-induced diabetic rats. The extracts were also subjected to phytochemical analyses. Results With an acute dose (1 g/kg), the methanol extracts showed significant reduction (31%) in fasting blood glucose (FBG) of the streptozotocin-induced diabetic rats. The FBG-decreasing effect of ethyl acetate extract was more rapid than that of the other extracts; the decreasing rates were 20% after 2 h, 21% after 3 h, and 8% after 5 and 7 h. After 7 h (31%), the effect of methanol extract on FBG was significantly lower than that of metformin. In the subcutaneous glucose tolerance test, only methanol and hexane extracts showed the similarity of metformin in diabetic rats. After 14 days, the effects of these extracts were similar to those of metformin (63.33%). The total flavonoid and phenolic contents of extracts decreased as the polarity of the extraction solvent increased. Conclusions The results obtained provide support for a possible use of O. tenuiflorum leaves in managing hyperglycemia and preventing the complications associated with it in type 2 diabetic.

Review on Polygonum minus. Huds, a commonly used food additive in Southeast Asia.

Polygonum minus (Polygonaceae), generally known as 'kesum' in Malaysia is among the most commonly used food additive, flavoring agent and traditionally used to treat stomach and body aches. Raw or cooked leaves of P. minus are used in digestive disorders in the form of a decoction and the oil is used for dandruff. The pharmacological studies on P. minus have demonstrated antioxidant, in vitro LDL oxidation inhibition, antiulcer activity, analgesic activity, anti-inflammatory activity, in vitro antiplatelet aggregation activity, antimicrobial activity, digestive enhancing property and cytotoxic activity. The spectroscopic studies of essential oil of P. minus showed the presence of about 69 compounds, which are responsible for the aroma. The phytochemical studies showed presence of flavonoids and essential oils. This review is an effort to update the botanical, phytochemical, pharmacological and toxicological data of the plant P. minus.

New cholinesterase inhibitors from Garcinia atroviridis.

A triflavanone, Garcineflavanone A (1) and a biflavonol, Garcineflavonol A (2) have been isolated from the stem bark of Garcinia atroviridis (Clusiaceae), collected in Peninsular Malaysia. Their structures were established using one and two-dimensional NMR, UV, IR and mass spectrometry and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Molecular docking studies of the isolated compounds were performed using docking procedure of AutoDock to disclose the binding interaction and orientation of these molecules into the active site gorge.

Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts

<p><b>OBJECTIVE</b>To study the antidiabetic activity of Gynura procumbens (G. procumbens) used in the traditional management of diabetes in Southern Asia.</p><p><b>METHODS</b>G. procumbens leaves were extracted sequentially with graded percentage of ethanol in water (95%, 75%, 50%, 25% and 0%), and the extracts were tested for antidiabetic activity using acute (7 h), subcutaneous glucose tolerance test and sub-chronic (14 d) test in non-diabetic and streptozotocin-induced diabetic rats. The extracts were further subjected to phytochemical studies.</p><p><b>RESULTS</b>In acute dose (1 g/kg), the extracts significantly lowered fasting blood glucose (FBG) in streptozotocin-induced diabetic rats (P<0.05). However, the FBG-lowering effect of the 25% extract compared to the other extracts, was rapid (47% after 2 h) and the highest: 53%, 53% and 60% in the 3rd, 5th, and 7th h, respectively (P<0.05), comparable only to the effect of metformin. Furthermore, the extracts suppressed peak FBG in subcutaneous glucose tolerance test, but only the 0% and 25% extracts, and metformin sustained the decrease until the 90th min (P<0.05). Moreover, in the 14 days study, the 25% extract exerted the highest FBG-lowering effect, namely 49.38% and 65.43% on days 7 and 14, respectively (P<0.05), similar to the effect of metformin (46.26% and 65.42%). Total flavanoid and phenolic contents in the extracts were found to decrease with increase in polarity of extraction solvents. The composition of reference compounds (chlorogenic acid, rutin, astragalin and kaempferol-3-O-rutinoside) followed a similar trend.</p><p><b>CONCLUSIONS</b>G. procumbens contains antidiabetic principles, most extracted in 25% ethanol. Interaction among active components appears to determine the antidiabetic efficacy, achieved likely by a metformin-like mechanism.</p>