Dual mechanisms of a Sri Lankan traditional polyherbal mixture in the improvement of pancreatic beta cell functions and restoration of lipoprotein alterations in streptozotocin induced diabetic rats.

Traditional polyherbal preparations have been utilized in Sri Lanka since ancient times and have gained a wide acceptance throughout the country. Although an extensive body of evidence supports the use of traditional herbal mixtures in the treatment of diabetes mellitus, only a few polyherbal mixtures have been subjected to systematic scientific investigations and their mechanisms for long-term glucose control remain unclear. In general, scientific evaluations of the effectiveness of antidiabetic formulations which are prescribed by traditional practitioners have received great attention, and therefore uncovering their mechanism of action would be beneficial. The aim of the present study was to investigate the therapeutic efficacy, in terms of antidiabetic and antihyperlipidaemic activities, of a well-known traditional polyherbal mixture composed of leaves of Murraya koenigii L., -cloves of Allium sativum L., - fruits of Garcinia quaesita Pierre and seeds of Piper nigrum L. in streptozotocin induced diabetic rats. Equal amounts from each of the above plant parts (100 g) were mixed together and extracted into cold water, hot water (3 h, refluxed) and water-acetone (1:1) separately. Dose response study of cold water, hot water, and water-acetone extracts of the polyherbal mixture at three selected doses of 0.5 g/kg, 1.0 g/kg and 1.5 g/kg was conducted in streptozotocin (STZ) induced diabetic rats. Based on the dose response data, hot water and water-acetone extracts at the therapeutic dose of 1.0 g/kg were administered to STZ induced diabetic rats (n = 6/group) daily for 30 days in the long-term study. Glibenclamide (0.5 mg/kg) was used as the positive control. Glycaemic parameters, pancreatic β cell restoration, and lipid profile were evaluated in diabetic rats treated with the plant extract mixture. HPLC fingerprints of hot water and water-acetone extracts of the polyherbal mixture were compared with those of extracts of individual plants with the respective solvents, in the standardisation protocol. The hot water and water-acetone extracts were shown to be active in the dose response study and 1.0 g/kg was selected for the long term study. Treatment with the hot water and water-acetone extracts of the polyherbal mixture and glibenclamide significantly lowered the glycated haemoglobin by 19%, 26%, and 43%, respectively, at the end of the intervention (p < 0.05). The serum insulin concentration was significantly increased (p < 0.05) upon the plant treatment, corroborating the evidence of β-cell restoration in the pancreas of H and E stained sections. Moreover, the above extracts reported an impressive restoration of lipoproteins in diabetic rats compared to the diabetic control rats. The homeostatic assessment of β-cell functions (HOMA-β) was also improved in rats treated with the hot water and water-acetone extracts of the polyherbal mixture. The HPLC fingerprints of the polyherbal mixture and the individual plants showed shifts in some peaks and formation of new peaks. The results revealed that the aforementioned polyherbal mixture possesses potent antihyperglycaemic and antihyperlipidaemic effects with considerable restoration of pancreatic β-cells, justifying the traditional use of the mixture in diabetes associated dyslipidaemia.

Liyanagamage DSNK ，Jayasinghe S ，Attanayake AP ，Karunaratne V ... -  《-》

Acute and Subchronic Toxicity Profile of a Polyherbal Drug Used in Sri Lankan Traditional Medicine.

A polyherbal drug composed of leaves of Murraya koenigii L. Spreng, cloves of Allium sativum L., fruits of Garcinia quaesita Pierre, and seeds of Piper nigrum L. is a popular drug which has been used by indigenous practitioners in Sri Lanka for the treatment of diabetes mellitus and dyslipidemia. The acute toxicity assessment was conducted, following a single oral dose of 0.25-2.0 g/kg in healthy rats, and rats were observed up to 14 days. The hot water extract (1.0 g/kg) and the water : acetone extract (0.5, 1.0, and 1.5 g/kg) were administered to Wistar rats for 28 days in the subchronic study. Hypoglycemic and antihyperglycemic activities (dose response studies) of cold water, hot water, and water : acetone extracts of the polyherbal mixture were evaluated at the doses of 0.5, 1.0, and 1.5 g/kg in healthy and streptozotocin-induced diabetic rats (70 mg/kg, ip), respectively. Acute toxicity study showed that the polyherbal drug did not cause any change in animals throughout the experimental period of 14 days. The administration of the hot water extract and the water : acetone extract of the polyherbal drug for 28 days did not produce changes in the selected biochemical and hematological parameters in Wistar rats (p > 0.05). The histological assessment corroborated the biochemical findings with no significant treatment-related changes in the kidney and liver. The treatment of polyherbal drug significantly lowered the serum glucose concentration compared to the diabetic control rats (p < 0.05) while it did not lead to a severe reduction of glucose concentration in healthy rats. The hot water and water : acetone extracts of the polyherbal drug showed a statistically significant improvement on total area under the glucose tolerance curve in diabetic rats (p < 0.05), reflecting dose-dependent antihyperglycemic effects of the drug. Based on the results, we conclude that the aforementioned antidiabetic polyherbal remedy is free of toxic/adverse effects at the equivalent human therapeutic dose in healthy Wistar rats and would be a safe therapeutic agent for long-term treatments.

Liyanagamage DSNK ，Jayasinghe S ，Attanayake AP ，Karunaratne V ... -  《-》

Antidiabetic, antihyperlipidaemic, and antioxidant activity of Syzygium densiflorum fruits in streptozotocin and nicotinamide-induced diabetic rats.

Krishnasamy G ，Muthusamy K ，Chellappan DR ，Subbiah N ... -  《-》

Polyherbal mixture ameliorates hyperglycemia, hyperlipidemia and histopathological changes of pancreas, kidney and liver in a rat model of type 1 diabetes.

One of the commonly prescribed 'anti-diabetic' polyherbal mixtures by European herbalists is made of Rubus fruticosus and Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods. This study aimed to evaluate the phytochemical composition, antioxidant capacity, potential toxicity, hypoglycemic, hypolipidemic, nephroprotective and hepatoprotective activities of this polyherbal mixture decoction. The phytochemical composition was evaluated using HPLC-UV. The antioxidant activity was assessed using the DPPH test. Potential toxicity was evaluated using the acute and sub-chronic oral toxicity method. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate (150 mg/kg). The animals whose blood glucose was >20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, D-10 and D-20 groups were treated with the polyherbal mixture (10 and 20 g of dry plant material/kg, respectively). I and M were control groups treated with insulin glargine (13 IU/kg) and metformin (150 mg/kg), respectively. Healthy control (HC) and diabetic control (DC) groups were treated with water. The blood glucose level was measured on days 14, 21 and 28. Lipid profile analysis was done on day 28. Pancreas, kidney and liver histopathology was evaluated using the H&E and Masson's trichrome staining. The liver tissue was additionally tested for PAS-positive cells. The HPLC-UV analysis revealed the presence of quinic, gallic and caftaric acid, arbutin, rutin, trifolin, astragalin, hyperoside, isoquercetin and quercitrin. The antioxidant activity of the extract was higher than the reference's one (p < 0.01). Treatment with the polyherbal mixture (10 and 20 g/kg) has shown no toxic effects. No major decline in blood sugar was recorded in I and M groups compared to the DC one (22.86 ± 2.58, 28.5 ± 0.42 and 27.82 ± 0.9 mmol/L, respectively). The polyherbal mixture lowered the blood glucose level to the normal value (8.64 ± 4.09, 5.26 ± 1.3 and 6.76 ± 1.54 mmol/L in D-10, D-20 and HC groups, respectively). Furthermore, it decreased the levels of total cholesterol, triglycerides, VLDL, LDL, atherogenic and cardiovascular risk indices (p < 0.001) compared to the DC group. In addition, the extract restored histopathological changes of the pancreas, kidneys and liver to the healthy animal level. Treatment with the polyherbal mixture extract was more effective than the standard drugs (insulin and metformin) in the amelioration of hyperglycemia, hyperlipidemia, and histopathological changes of the pancreas, kidney and liver tissue.

Madić V ，Petrović A ，Jušković M ，Jugović D ，Djordjević L ，Stojanović G ，Vasiljević P ... -  《-》

Comparison of the Efficiency of Lepidium sativum, Ficus carica, and Punica granatum Methanolic Extracts in Relieving Hyperglycemia and Hyperlipidemia of Streptozotocin-Induced Diabetic Rats.

Ramadan S ，Hegab AM ，Al-Awthan YS ，Al-Duais MA ，Tayel AA ，Al-Saman MA ... -  《-》