Formulation and evaluation of SGLT2 inhibitory effect of a polyherbal mixture inspired from Ayurvedic system of medicine.

Background and aim: The ingredients viz., Artemisia roxburghiana, Cissampelos pareira, Stephania glabra, Drimia indica, Roylea cinerea, Tinospora sinensis and Curcuma longa of the present formulation are used to treat diabetes in the Indian traditional medical system. Adopting the concept of multiple herbal mixtures for better therapeutic effects from the ancient Ayurvedic text Sarangdhar Samhita, the present study aimed to develop a polyherbal formulation (PHF) of seven herbs and to evaluate its sodium-glucose cotransporter protein-2 (SGLT2) inhibitory effect on type 2 diabetic rats. Experimental procedure: Streptozotocin (STZ) (60 mg/kg) and nicotinamide (NAM) (120 mg/kg) were intraperitoneally administered to induce type 2 diabetes in Wistar rats. The animals were divided into 5 groups viz. normal control, diabetic control, positive control (dapagliflozin at 0.1 mg/kg) and two test groups (PHF at 250 and 500 mg/kg). Various parameters including blood glucose, serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), bilirubin, triglycerides and creatinine were measured. Results and conclusion: The treatment with PHF (250 and 500 mg/kg) showed a significant (p < 0.05) decrease in blood glucose levels by 56.37% and 58.17%, respectively. The levels of SGOT, SGPT and bilirubin were significantly reduced in PHF-fed diabetic rats. Histopathological examination revealed no major changes in the treated groups as compared to the normal control. The molecular docking study showed strong binding of ß-sitosterol, insulanoline, warifteine, dehydrocorydalmine, taraxerol acetate, lupeol, corydalmine and luteolin to SGLT2 protein. The present study concludes that PHF has promising antidiabetic activity via inhibiting SGLT2 protein without showing any adverse effects.

A gastroretentive drug delivery system of lisinopril imbibed on isabgol-husk.

The gastroretentive drug delivery system is site-specific and allows the drug to remain in the stomach for a prolonged period of time so that it can be released in a controlled manner in gastrointestinal tract. The present study was carried out to develop a gastroretentive drug delivery system using isabgol as an excipient to prolong the residence time of the model drug lisinopril in the stomach. The gastroretentive ability of isabgol was increased by addition of NaHCO3 as a gas-generating agent while its mucoadhesive property was enhanced by incorporation of HPMC-K4M. The drug, NaHCO3 and HPMC-K3M were imbibed on isabgol-husk as per entrapment efficiency of the isabgol-husk. After drying, the product was filled in a hard gelatin capsule and evaluated for its buoyancy, mucoadhesive properties, swelling index and in vitro drug release. The lisinopril released through isabgol was delayed by 12 hours when compared to a preparation available on the market which released the complete drug in 0.5 hours. The drug release study of lisinopril from the formulation follows first order kinetics using a diffusion controlled mechanism. The results from the present study revealed that isabgol can be used as a potential excipient for the formulation of gastroretentive drug delivery systems in the near future.

Chemical constituents from the stem bark of Symplocos paniculata Thunb. with antimicrobial, analgesic and anti-inflammatory activities.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Symplocos paniculata Thunb. has been used to check abortion in folk medicine in India. AIM OF THE STUDY: The present study was undertaken to isolate the phytochemicals from the plant together with the evaluation of antimicrobial, analgesic and anti-inflammatory activities of the plant extract and isolated compounds. MATERIALS AND METHODS: The plant extract was subjected to column chromatography for isolation of phytochemicals. The agar diffusion method was adopted for antimicrobial activity to determine MICs. Ethanolic extract and isolated compounds were selected for investigating their analgesic activity on acetic acid-induced writhing response in mice. The anti-inflammatory activity was performed on carrageenan-induced paw edema in rats. RESULTS: The stem bark of the plant afforded seven compounds, 4-(8-hydroxyethyl) cyclohexan-1-oic acid (1); androst-5(6)-ene 17-one 3ß-O-(ß-d-glucopyranoside) (2); 9ß,25-cyclo 3ß-O-(ß-D glucopyranosyl)-echynocystic acid (3); 9ß,19-cyclo 24-methylcholan-5,22-diene 3ß-O-{ß-D-glucopyranosyl (1→6) α-L-rhamnopyranoside} (4); 30-ethyl 2α,16α-dihydroxy 3ß-O-(ß-D-glucopyranosyl) hopan-24-oic acid (5); 32,33,34-trimethyl-bacteriohopan-16-ene 3-O-ß-D-glucopyranoside (6) and flavone 3',4',5',6-tetramethoxy 7-O-ß-D-glucopyranosyl (1→3) ß-D-glucopyranoside (7). The extract and isolated compounds exhibited antimicrobial, analgesic and anti-inflammatory activities. CONCLUSION: The present study concludes that ethanolic extract of the plant and its constituents having significant antimicrobial, analgesic and anti-inflammatory activities.

The genus Stephania (Menispermaceae): chemical and pharmacological perspectives.

The plants of the genus Stephania (Menispermaceae) are widely distributed, and have long been used in folk medicine for the treatment of various ailments such as asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Over 150 alkaloids together with flavonoids, lignans, steroids, terpenoids and coumarins have been identified in the genus, and many of these have been evaluated for biological activity. This review presents comprehensive information on the chemistry and pharmacology of the genus together with the traditional uses of many of its plants. In addition, this review discusses the structure-activity relationship of different compounds as well as recent developments and the scope for future research in this aspect.

Anti-hyperglycemic effect of 11-hydroxypalmatine, a palmatine derivative from Stephania glabra tubers.

A palmatine derivative, named 11-hydroxypalmatine (4), has been isolated from the tubers of Stephania glabra, together with three known alkaloids, palmatine (1), dehydrocorydalmine (2), and stepharanine (3). The structures of the compounds were elucidated by means of spectroscopic analysis including 2D NMR experiments. The hypoglycemic activity of 4 was evaluated against alloxan-induced diabetic mice. The test compound was administered at doses of 25, 50, and 100 mg/kg, p.o., 36 h after alloxan injection (60 mg/kg, i.v.). The alloxan-induced diabetic mice showed significant reduction in blood glucose after treatment with the test compound by 52% as compared to the positive control glibenclamide (54%) and the diabetic control (27%).