Evaluation of anti-nociceptive and anti-inflammatory activities of Piper sylvaticum (Roxb.) stem by experimental and computational approaches Abstract Piper sylvaticum Roxb., (Family: Piperaceae), commonly known as pahaari peepal, is used in traditional medicine for the treatment of rheumatic pain, headache, asthma, chronic cough, diarrhea, and wounds. To provide scientific proof for its traditional use, the present study was designed to investigate the antinociceptive and anti-inflammatory properties of methanol extract of P. sylvaticum stem (MEPSS) in pain models. Additionally, computational studies viz. molecular docking, ADME and toxicological property predictions were performed to identify the potent phytochemicals of this plant for antinociceptive and anti-inflammatory activities with good oral bioavailability and safety features. Quantitative phytochemical analysis of MEPSS was performed using established protocols. The antinociceptive activity was determined using acetic acid and formalin test in mice at the doses of 200 and 400 mg/kg while paw edema induced by carrageenan used for anti-inflammatory activity. Molecular docking study was performed by Schrödinger Maestro 10.1 whereas the SwissADME and admetSAR were used for ADME and toxicity prediction respectively. The total phenolic and flavonoid contents of MEPSS were 93.39 and 53.74 mg gallic acid and quercetin equivalent/g of extract respectively. The methanol extract exhibited significant and dose-dependent antinociceptive and anti-inflammatory effects in experimental pain models. Also, our docking study showed that piperine, piperlonguminine, and sylvamide have the best binding affinities to cyclooxygenase enzymes with good ADME/T properties. This study confirmed that MEPSS possess significant antinociceptive and anti-inflammatory activities which could be due to the presence of phytochemicals and three bioactive compounds (piperine, piperlonguminine, and sylvamide) were found to be most effective in computational studies.

Natural products and their active principles used in the treatment of neurodegenerative diseases: a review Abstract Free radicals are the byproducts of physiological aerobic cellular metabolism. Intrinsic antioxidant system plays its pivotal function in prevention of any loss due to free radicals. Though, incorporation or excess production of free radicals from environment to living system or imbalanced defense mechanism of antioxidant system leads to severe consequences like neuro-degeneration. Sensory or functional loss occurs in neural cells in neurodegenerative diseases. Besides numerous other genetic or environmental factors, oxidative stress is the major cause which leads to damage of neurons and production of neurodegenative diseases. However, oxygen is vital for existence, excessive reactive oxygen species production and imbalanced metabolism leads to a variety of diseases such as aging, Parkinson’s disease, Alzheimer’s disease, and many other neurodegenative diseases. Free radicals toxicity contributes to DNA and proteins damage, tissue damage, inflammation and consequent cellular apoptosis. Neuroprotection is a broad term commonly used to refer therapeutic strategies that can prevent, delay or even reverse neuronal damage. Since thousands of years, lots of medicinal plants have been used in a group of herbal preparations of Ayurveda (Indian traditional health care system) named Rasayana because of the antioxidant principles present in it, responsible for their medicinal use in neurodegenerative diseases. This work constitutes a literature review on natural products contain antioxidant principles used in the treatment of neurodegenerative disease.

Anticancer effect of some fruits peels aqueous extracts Abstract Fruits peels are considered one of the most waste products of food industry. In this paper we attempt to get useful of these peels with low cost methods. We prepared aqueous extract of peels of apple, banana, guava, kiwi, lemon, mango, orange, papaya, pomegranate and watermelon. The anticancer activity of the extracts against different cell lines was examined using the cell viability test using MTT assay. The aqueous extract of peels of banana, pomegranate, orange and lemon showed the highest anticancer activity against the tested cell lines [pancreatic (AsPC1), breast (MCF7) human cancer cell lines colon cancer cell line (HCT116), larynx cancer cell line (HEP2) and liver cancer cell line (HEPG2)], as they have high antioxidant capacity. Beside that these peels extract contain high content of very important pharmaceutical compounds such as alkaloid, tannin, saponin, steroid, glycosidic cyanide, phytate, phenolic and flavonoid. Kiwi and watermelon peels extract did not show any anticancer activity against the different tested cell lines. Also they have the lowest antioxidant and pharmaceutical compounds content.

Correction to: Antioxidant and anti-inflammatory properties Hymenodictyon excelsum bark Unfortunately, one of the co-authors’ given name was incorrect in the original version of this article. The correct given name should be: Sanjib.

The effect of coverage structure of private health insurance on physician visits between conventional and traditional medicine Abstract Private health insurance is especially fundamental to medical care accessibility in Korea where the share of government medical expenditure is low. Private health insurance covers out-of-pocket costs for all conventional medicine but not for all traditional medicine. This study empirically explores the possibility that Korea’s unique coverage structure of private health insurance causes conventional medicine to be more accessible than traditional medicine. A zero-inflated negative binomial model for 83,238 participants obtained from the Korean Health Panel was applied. The accessibility to conventional and traditional medicine between individuals with and without FFS-PHI was compared by employing the number of physician visits as the measurement of accessibility. Regression results present that having fee-for-service private health insurance increases the incident rate for conventional physician visits by 6.6% (p < 0.01). However, there is not a significant variation in the number of traditional physician visits between people with and without fee-for-service private health insurance. Considering the demand and effectiveness of traditional medicine, the findings support policy changes to the Korean medical care coverage structure that create more equitable accessibility to traditional medicine.

Prostaglandin E 2 and oxidative defense system contributed to anti-nociception action of aqueous Adansonia digitata bark extract in induced neuropathic pain in Wistar rats Abstract Diverse etiology of neuropathic pain conditions demands new understanding of its pathogenesis and development of effective therapy. Treatment of induced neuropathic pain using aqueous Adansonia digitata bark extract has not been investigated. We probed the systemic administration effects of A. digitata bark extract on sciatic nerve ligated induced neuropathic pain. Treatments with extract caused increased pain threshold on hot plate, hot- and cold-immersion test. Notably, an apparent decreased in systemic prostaglandin E2 occurred concurrently with strengthened oxidative defense system. By contrast, extract-hexamethonium, -propranolol, -atropine or -prazosin cotreatments in induced-neuropathic rats suggested no involvement of muscarinic, nicotinic, beta or alpha-1 receptors in the analgesic action of the extract. Though, a weaken oxidative defense system was observed based on oxidative markers measured. These results indicate the crude extract ability to induce pain relief in neuropathic pain and this coincides with degree of decreased PGE2 and increased antioxidants as well as decreased lipid peroxidation product. This is the first report demonstrating the usefulness of aqueous A. digitata bark extract in the management of neuropathic pain, an action that involves alteration of PGE2 and oxidative defense system. Graphical abstract

Comparative potential of Simvastatin, Rosuvastatin and Fluvastatin against bacterial infection: an in silico and in vitro study Abstract In the current investigation, we have compared the potential of statin drugs (Simvastatin, Rosuvastatin and Fluvastatin) as potential anti-bacterial agent by conducting in silico, in vitro and ex vivo studies. In silico study was conducted to check the interaction of statin drugs towards various targets of bacteria. The percentage growth retardation, bacterial growth kinetics, MIC determination, post antibiotic effect and biofilm formation assay were conducted to check the anti-bacterial effect of statin drugs under in vitro conditions. Finally, MTT assay was used to check the percentage of immune cell viability after Simvastatin treatment. Docking studies have revealed good interaction of Simvastatin, Rosuvastatin and Fluvastatin towards various targets of bacterial strains as that of the internal ligand. Simvastatin has shown good antibacterial activity against S. aureus, B. pumilus, P. aeruginosa and S. enterica as compared to Rosuvastatin and Fluvastatin. In vitro results have shown concentration and time dependent inhibition of bacterial growth by Simvastatin in concentration range of 64–256 μg/ml. Finally, MTT assay have shown non-cytotoxic effect of Simvastatin against adaptive immune system. In conclusion, Simvastatin could be a potential candidate as an anti-bacterial agent against a wide range of bacterial infections. However, further studies are required to check its complete role before starting phase I clinical trial.

Squill ( Drimia maritima L.) and its novel biological activity Abstract Squill (Drimia maritima L.) as well- known medicinal plants from ancient times has been used for treatment of different ailments. This review article evaluated a comprehensive investigation on squill in modern medicine and its relation to traditional believes. The information were extracted from accessible resources (PubMed, Wiley, Springer, and Google) and Persian and English traditional books. Squill was traditionally used as good remedy for cough, asthma, indigestion, alopecia, pain and lice. Modern clinical studies confirmed the traditional believes on squill in treatment of nonalcoholic fatty liver, asthma, head lice, alopecia and inflammatory pains. Also, the antioxidant, anti-parasite, anti-cancer and insecticidal effects of squill have been confirmed in experimental studies. The results of investigations exhibited that squill had good potency in management of respiratory and gastrointestinal diseases, therefore, it can be more considerate in clinical future.

Effects of different extraction solvents on polyphenols and antioxidant capacity of peel, pulp and seed kernel of kuini ( Mangifera odorata ) Abstract This study aimed to investigate the effect of different extraction solvents and determine the optimum solvent concentration (in the range of 0–100%) for the recovery of total phenolic content, total flavonoid content and antioxidant capacity of peel, pulp and seed kernel of Mangifera odorata fruit. The total phenolic (TPC) and total flavonoid content (TFC) were determined using Folin–Ciocalteu and aluminum chloride assays, respectively. The highest level of TPC was found in 60% and 80% (v/v) acetone for pulp and seed kernel while peel showed the highest TPC at the concentration of 80% (v/v) acetone. The optimum total flavonoid content was achieved at 100% (v/v) methanol for all fruit parts. Antioxidant activity was measured using ferric reducing antioxidant power assay, and the result showed the highest activity at 60% (v/v) ethanol for all parts of M. odorata fruit. The highest scavenging activity was shown at 60% (v/v) acetone for pulp and seed kernel, respectively. Peel exhibited the highest scavenging activity at 40% acetone. It can be concluded that the recovery of phenolic compounds was dependent on the polarity of the chemical constituents in the different parts of fruit as well as the polarity of the solvent systems used. Seed kernel had the highest TPC, TFC and possessed excellent antioxidant capacity compared to peel and pulp of M. odorata. Therefore, the seed kernel can be incorporated into food products as a functional ingredient for the prevention of oxidative-stress related diseases.

Curcuma zedoaria (christm.) roscoe inhibits proliferation of MDA-MB231 cells via caspase-cascade apoptosis Abstract Curcuma zedoaria is a perennial herb that belongs to Zingiberaceae family, found growing lavishly in Manipur; a north eastern part of India. The traditional usages of the plant is not limited to a particular disease but extended over a large number of diseases. Anti-breast cancer activity of ethyl acetate extract of Curcuma zedoaria was conducted on MDA-MB231 breast cancer cell line with the help of MTT assay technique and the mechanistic pathway was established with the help of western blot technique, confocal microscopy, wound healing migration assay and cell cycle analysis. Cell cytotoxicity test of ethyl acetate extracts showed remarkable result on MDA-MB231 in dose dependent manner (p < 0.05). Confocal microscopy studies on MDA-MB231 cells revealed the activation of cleaved caspase 9 in treated cells. Western blot analyses confirm the regulation of cytochrome C and suppression of Bcl-2 in treated cells which suggest ethyl acetate extract of Curcuma zedoaria inhibits the cancer cells through cascase-dependent pathways. In cell cycle analysis, after the treatments of the cells; there was an increase in the percentage of SubG0/G1 cells that decreased S and G2 phase indicating the population undergoing cell death (apoptosis or necrosis) thereby, our data suggest that ethyl acetate extracts were able to induce significant apoptosis in MDA-MB-231 cells in dose dependent manner. The wound healing migration assay confirms the anti-metastatic nature of the plant extract. With the help one way ANOVA test, all the experiments were executed and it was found that ethyl acetate extract of Curcuma zedoaria inhibits MDA-MB231 cells with the down-regulation of the expression of Bcl-2 through cascase-dependent pathways therefore Curcuma zedoaria is a potent anti-cancer plant especially in breast cancer.