Essential Oils Downregulate Pro-Inflammatory Cytokines and Nitric Oxide-Mediated Oxidative Stress in Alloxan-Induced Diabetogenic Rats.

INTRODUCTION: Hyperglycemia is associated with an elevated level of reactive nitrogen species (RNS) that leads to nitrosative stress and exacerbates the progression of diabetic complications. METHODS: Present study was aimed to evaluate the therapeutic effects of essential oils (EOs) on increased serum levels of nitric oxide (NO) in diabetogenic rats. Diabetogenic rats were treated with EOs separately and/or in combination at the dose of 100 mg/kg, orally for one month. Blood sampling was done at the 1st, 15th and 30th day of the treatment period to investigate the effect of treatment on biomarkers of diabetic complications. RESULTS: In diabetogenic rats, serum levels of NO, malondialdehyde (MDA) and pro-inflammatory cytokines were significantly increased when compared with that of the control group. Whereas, diabetogenic rats treated with EOs decreased serum levels of NO, MDA and pro-inflammatory cytokines up to a significant extent when compared with that diabetogenic rats treated with the standard antidiabetic drug. Moreover, EOs also increased insulin sensitivity in peripheral tissues and insulin secretion from ß-cells of pancreatic islets more efficiently when compared with that of diabetogenic rats. Additionally, it was also found that EOs improved lipid profile and normal functions of kidney and liver as compared to that of diabetogenic rats. CONCLUSION: Findings of this study indicate that EOs may reduce pro-inflammatory cytokine levels by modulating the expression of NO. EOs may also ameliorate the nitrosative stress and maintain glucose homeostasis that are major culprits of diabetic complications.

Anti-angiogenesis Potential of Phytochemicals for the Therapeutic Management of Tumors.

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models. The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.

Anti-Ulcerogenic Effects of Salmalia Malabarica in Gastric Ulceration--Pilot Study.

BACKGROUND: According to an estimation of the WHO, almost 80% of people globally are treated by traditional medicine. OBJECTIVES: We evaluated the anti-ulcerogenic potential of Salmalia malabarica extract in rats using aspirin-, alcohol- and pylorus ligation-induced ulcer models. MATERIAL AND METHODS: Two different doses (200 and 400 mg/kg body weight) of Salmalia malabarica extract was administered intraperitoneally (i.p.) to all 3 ulcer-induced models for 5 consecutive days. The anti-ulcerogenic potential in rats treated with 2 doses of Salmalia malabarica extract and omeprazole (20 mg/kg, i.p.) was determined and compared to the control groups. RESULTS: Salmalia malabarica extract showed a significant decrease in ulcer index as compared to the control group in a dose-dependent manner. Salmalia malabarica extract also showed protection of 66.22% and 74.54% in asprin-, 73.79% and 78.14% in alcohol- and 68.94% and 78.84% in pylorus ligation-induced ulcers. However, omeprazole showed protection of 84.73%, 85.5% and 86.12% in aspirin-, alcohol- and pylorus ligation-induced ulcers, respectively. Furthermore, Salmalia malabarica extract significantly decreased the volume of gastric juice, free and total acidity, whereas it increased gastric pH when directly compared to the control group. CONCLUSIONS: Conclusively, Salmalia malabarica possesses anti-ulcerogenic, antisecretory, and cytoprotective potential and can be used as a supplement for the treatment of gastric ulcers in a dose dependent manner.

The Analgesic, Anti-Inflammatory and Anti-Pyretic Activities of Tinospora cordifolia.

BACKGROUND: Tinospora cordifolia (T. cordifolia) is a valuable resource due to its traditional uses in the treatment of pain, fever and inflammation, but no sufficient scientific literature is available online to confirm its traditional uses in these ailments. OBJECTIVES: This study was carried out to validate the traditional uses of T. cordifolia in treating pain, inflammation and pyrexia, using albino mice as an experimental animal model. MATERIAL AND METHODS: The analgesic effects of T. cordifolia extract were assessed by using the acetic acid-induced writhing test, hot plate test and tail-flick test. The carrageenan test was performed to assess anti-inflammatory potential, and anti-pyretic activity was evaluated by the brewer's yeast-induced pyrexia method. RESULTS: The results showed that the T. cordifolia extract exhibited significant analgesic effects in a dose-dependent manner in the three pain models tested. The extract also exhibited significant anti-inflammatory effects in the carrageenan-induced inflammation test and antipyretic effects in the brewer's yeast-induced pyrexia test in dose-dependent manner compared to the effects observed in the control group animals. CONCLUSIONS: From the findings of the present study, it can be concluded that T. cordifolia extract has strong analgesic, anti-inflammatory and anti-pyretic effects. Further studies are required to investigate the therapeutic activities of the phytochemical constituents of T. cordifolia against pain, inflammation and pyrexia.

Effect of HA14-1 on apoptosis-regulating proteins in HeLa cells.

Overexpression of Bcl-2 has been recognized in various malignancies. Recently, HA14-1, a Bcl-2 antagonist, has been identified for its anti-apoptotic effect. However, mode of action of HA14-1 still remains to be elucidated. In this study, we examined HA14-1 binding efficiency with receptor proteins through molecular docking. Cell viability using HeLa cells was evaluated through MTT assay after exposure to different concentration of HA14-1. Moreover, after HA14-1 exposure, expressions of tumor suppressor protein (p53), BH3-only protein (Puma) and apoptosis-associated proteins were analyzed by Western blotting. From the results, it was found that HA14-1 occupied all three domains; BH1, BH2, and BH3 within the hydrophobic pocket of Bcl-2. However, HA14-1 occupied only BH1 and BH3 of Bcl-xl, conversely, no such stable bond was observed for Bax and Bak. ARG107 and TYR101 were the amino acids involved in the binding of HA14-1 to Bcl-2 and Bcl-xl, respectively. Additionally, decrease in Bcl-2 and Bcl-xl expression along with increase in p53 and Puma expression after exposure to HA14-1 was observed. The results suggested p53 pathway to be the probable mechanism of action for the induction of apoptosis in HeLa cell by downregulating the effect of anti-apoptotic proteins suggesting that HA14-1 may provide therapeutic potential for the treatment of human cervical cancer.