Khalid Ghazanfar

Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition

Diabetes mellitus is increasing at an alarming rate and has become a global challenge. Insulin resistance in target tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes (T2D). Chronic low-grade inflammation in T2D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction. Many factors advocate a causal link between metabolic stress and inflammation. Numerous cellular factors trigger inflammatory signalling cascades, and as a result T2D is at the moment considered an inflammatory disorder triggered by disordered metabolism. Cellular mechanisms like activation of Toll-like receptors, Endoplasmic Reticulum stress, and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2D with inflammation. This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2D by capturing relevant evidence from various sources. The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2D.

Antidiabetic Activity of Artemisia amygdalina Decne in Streptozotocin Induced Diabetic Rats

Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500 mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on β-cells of pancreas in diabetic rats. The current study revealed the antidiabetic potential of Artemisia amygdalina being effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use.

Scientific Validation of Gentiana kurroo Royle for Anti-Inflammatory and Immunomodulatory Potential

Gentiana kurroo Royle is a critically endangered medicinal plant species endemic to the northwestern Himalayas. This plant was studied for the immunomodulatory and anti-inflammatory potential. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts were found to be active against inflammation. The methanolic fraction was observed to be the most effective in inhibition of paw edema with the inhibitory potential of 47.62%. In immunomodulation studies the plant extracts showed the immunosuppressant activity. Methanolic fraction was observed to have maximum potential for the suppression of both humoral (57.57% and 54.05%) and cell mediated immunity (65.27% and 75%). From these studies, it can be concluded that the extracts of plant are having anti-inflammatory and immunosuppressant activity. Since in chronic inflammation like arthritis there is the involvement of immune system, this plant may serve as an alternative for the treatment of autoimmune diseases like arthritis.

Evaluation of Artemisia amygdalina D. for Anti-Inflammatory and Immunomodulatory Potential.

Artemisia amygdalina D. is a critically endangered endemic medicinal plant of Kashmir Himalayas. In the current study anti-inflammatory and immunomodulatory activity of the plant was carried out. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC-specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts used as test drugs showed to have anti-inflammatory potential. The methanolic fraction was observed to have the maximum effect on the inhibition of paw edema formation with the inhibitory potential of 42.26%, while in the immunomodulation studies the test drugs were found to have the immunosuppressant activity with methanolic fraction again showing the maximum potential for the suppression of both humoral (55.89% and 47.91%) and cell-mediated immunity (62.27% and 57.21%). The plant in total seems to have the anti-inflammatory potential. The suppression of immune system suggests some mechanistic way by which the inhibition of inflammation takes place. Since, in chronic inflammation like arthritis, there is the involvement of immune system, the plant in that way may serve as an alternative for the treatment of such autoimmune diseases.

Anti-inflammatory and immuno-modulatory studies on LC-MS characterised methanol extract of Gentiana kurroo Royle

BackgroundIn ayurvedic traditional medicine Gentiana kurroo Royle (family; Gentianaceae) is used to treat several metabolic diseases. This plant is rich in various compounds belonging to flavonoids and glycosides. Till now little work has been carried out on immunomodulatory and anti-inflammatory potential of this plant. This study confirms the presence of bioactive compounds and evaluates the anti-inflammatory and immunomodulatory effect of this plant.MethodsTo carry out this work, the methanol extract was investigated in different doses using in vivo and in vitro models. In vivo study involved haemagglutination titre and DTH methods, and in vitro study was done using splenocyte proliferation assay and LPS stimulated macrophage culture. TNF-α, IL-6 and NO were assayed using ELISA kit methods, while NF-κB was evaluated by western blotting. LC-ESI-MS/MS was used for the characterization of the methanol extract.ResultsThe results showed suppression of both humoral and cell mediated immunity in vivo. This effect was also observed by inhibition of B and T cell proliferation in splenocyte proliferation assay. TNF-α, IL-6 and NO concentrations were also less in extract treated macrophage cultures. The NF-κB expression was also lowered in treated macrophages as compared to untreated macrophages. All these observations were found to be dose dependent. LC-MS characterization of this extract showed the presence of known compounds which are glycosides, alkaloids and flavonoids in nature.ConclusionThe methanol extract of this plant was found to be rich in glycoside, alkaloid and flavonoid compounds. These compounds are probably responsible for the suppression of immune response and anti-inflammatory activity. The extract as such and identified bioactive compounds can be useful for the treatment of inflammatory disorders.

Acute and Sub-acute oral toxicity studies of Deedan-A Unani drug in Albino rats -

Abstract. Deedan is a very effective compound formulation of Unani System of medicine used for the treatment of worm infestation. The objective of this study was to investigate the Acute and Sub-acute toxicity of Deedan in Albino of both the sexes. In the acute toxicity study, Deedan was administered orally at the limit dose of 2000mg/kg b.w. to both male and female rats, and the animals were then observed individually 30 minutes, 4 hour post-doing, and at least once daily for next 14 days. In the Sub-acute toxicity study a limit dose of 1000 mg/kg body weight was administered orally in a single bolus everyday for 28 days. The rats were observed daily during the period of the study, and sacrificed on the 29th day. Observation parameters of the animals included a comparative evaluation of general appearance/behaviour, morbidity/mortality, body weights, food/water consumption, and haematology, biochemistry and histopathology of major organs of treated and control groups. There was no mortality, morbidity, or cage-side/laboratory findings of any adverse health effect in the treated animals in comparison to their respective controls in both toxicity studies. Deedan was thus found to be free of any toxic effects under the conditions of these studies.

Evaluation of Antiarthritic Potential of Methanolic Extract of Gentiana kurroo Royle.

Rheumatoid arthritis is a systemic disorder which involves the activation of immune system against the self-tissues. The main targets of this disease are the joints. Being systemic the development of this disease involves different mechanisms and thus the exact cause of this disease remains unknown. Although different drugs have been developed, none has been found to be the cure for this disease. In the current study the rat carrageenin paw was used as a model for acute inflammation and mycobacterium induced adjuvant arthritic model was used for exploring the antiarthritic potential of methanolic extract of Gentiana kurroo. In this study the different extracts tested showed less inhibition of acute inflammation than methanolic extract. The methanolic extract was further used in different doses and the anti-inflammatory efficacy was found to be dose dependent. The results obtained were significant with the control and the standard groups. In the arthritic model the methanolic extract showed decrease in the paw volume of arthritic animals and also in the arthritic symptoms. Again the results obtained were found to be significantly dose dependent. From the results obtained it can be concluded that this extract may serve as a source of drug against the rheumatoid arthritis.

9,10-seco-9,19-cyclolanostane triterpene from Salix caprea L. (Goat Willow)

Chemical investigation of low polar solvent extract of Salix caprea through chromatographic techniques led to the isolation of new triterpene as 1α,3β,25-trihydroxy-9(11)-ene-16-one-9,10-seco-9,19-cyclolanostane (1) along with fatty alcohols. The structure of compound 1 was established by IR, HRESI/MS and NMR including 1D and 2D experiments. The compound 1 showed moderate in vitro antiplasmodial activity.

Gentiana kurroo Royle attenuates the metabolic aberrations in diabetic rats; Swertiamarin, swertisin and lupeol being the possible bioactive principles

Abstract Background Gentiana kuroo Royle is a medicinally important plant of north-western Himalayas used for various ailments. In the present study, the plant extracts were investigated for the antidiabetic effects in streptozotocin-induced diabetic rats. Methods The impact of the extracts on serum glucose levels of diabetic rats was compared with reference drug – glibenclamide-treated diabetic rats. Streptozotocin injection was used to induce diabetes in fasted rats. Various biochemical, physiological and histopathological parameters in diabetic rats were observed for assessing the antidiabetic activity. Results The serum glucose concentrations in diabetic rats were significantly lowered by the extracts (methanolic and hydroethanolic at the doses of 250 and 500 mg/kg body weight). Several related biochemical parameters like creatinine, low-density lipoproteins, triglycerides, cholesterol, alkaline phosphatase, serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase were likewise decreased by the concentrates. The extracts also showed reduction in feed and water consumption of diabetic rats when compared with the diabetic control. The extracts were found to demonstrate regenerative/protective effect on β-cells of pancreas in diabetic rats. The methanolic and hydroethanolic extracts also exhibited hypoglycaemic effect in normal glucose-fed rats (oral glucose tolerance tests). LC-MS characterization of this extract showed the presence of these compounds – Swertiamarin, swertisin, lupeol, etc. Conclusions The current study demonstrated the counter diabetic capability of G. kuroo Royle being powerful in hyperglycaemia and can viably ensure against other metabolic deviations created by diabetes in rats. The possible bioactive principles responsible for the antidiabetic activity of G. kurroo Royle are Swertiamarin, swertisin and lupeol.

Sub-chronic oral toxicity study of Kushta Hajrul-Yahood (A Herbo-mineral Unani formulation) in Wistar rats

PD (Kushta Hajrul Yahood) is a Unani drug used for the treatment of renal and bladder calculi. The aim of the study was to demonstrate the scientific validity of detoxification method for preparation of Kushta and also to investigate the sub-chronic oral toxicity study of PD and CM (Crude material of Kushta Hajrul Yahood-its Un-detoxified form) in Wistar rats. Animals were orally treated once daily with test substance at the dose level of 1000mg and its two sub fractions 500 and 250mg/kg body weight for 90-days. Rats were observed throughout the study period. Body weight, feed and water consumption were recorded weekly. Overnight fasted rats were sacrificed on 91st day. Blood sample were collected for Haematological and biochemical studies. Organs were collected to record the organ weight and tissues for histology. The results showed elevation of liver enzymes due to the administration of PD at the dose level of 1000mg/kg body weight only, while-as in case of CM, there were significant elevation of liver enzymes at all the three doses. This elevation of enzymes also correlates with histopathological changes in liver tissues. This study concludes that the method of detoxification adopted for preparing Kushta substantially reduces the elements of toxicity.