Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols. AIM OF THE STUDY: This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). MATERIALS AND METHODS: In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å). RESULTS: EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κß and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam. CONCLUSIONS: Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.

Acacia modesta attenuates MnCl2 induced hepatotoxicity, oxidative stress and hepatic inflammation in wistar rats.

Natural Plants are broadly used in treating inflammatory disorders. The current study focused on evaluating the hepato-protective and anti-inflammatory potential of A. modesta in MnCL2 induced hepatotoxicity and liver inflammation. The MnCl2 induce 6.0mg/kg was given for 30 days (p.o) to induced hepatotoxicity and liver inflammation. The ethanolic extract of A. modesta were given orally at the dose of 100mg/kg/day. The in vivo inflammatory manganese induced hepatotoxic model is used for evaluating the acacia heap to-protective effect. Gas chromatography-mass spectrometry analyses were performed to find out compounds responsible for anti-inflammatory properties. Results showed that administration of ethanolic extract (100 mg/kg), altogether diminished inflammation of the liver, expanded liver capacity, oxidative stress and his to-pathological outcomes in the current study compared with disease rats. The beneficial outcomes of A. modesta extract were observed on liver inflammation.

A comprehensive review on gout: The epidemiological trends, pathophysiology, clinical presentation, diagnosis and treatment.

The current review was planned to assess updated knowledge about gout and to highlight the various areas which need to be focussed upon for better healthcare. Relevant articles published in English language were reviewed by utilising various databases including Google Scholar, Springer Link, Science Direct and MEDLINE. Data revealed a precipitating number of gout cases from the developed countries, while the developing countries on the other hand were found to be faced with an even higher threat. The risk factors and pathophysiology of gout are immaculate and clearly established. Hence, appropriate measures can be explored and worked on to pinpoint diagnosis, and economical treatment. In order to lessen the elevated global health burden along with revolutionising the patient's quality of life, an immediate action is required in certain aspects, like the adoption of a healthy modified lifestyle, a reduction in exposure to risk factors, robust prophylactic measures, bettering awareness, and an approach to early diagnosis followed by optimal treatment protocols.

Synergistic Effect of Barbadensis miller and Marsdenia Condurango Extracts Induces Apoptosis Promotes Oxidative Stress by Limiting Proliferation of Cervical Cancer and Liver Cancer Cells.

BACKGROUND: Drug synergy is the combine effect of drug efficacy. Synergistic combinations of active ingredients have proven to be highly effective and more useful in therapeutics. In contrast, the individual effect of drug is usually undesirable and mostly used for selecting drug-resistant mutations. Purpose of this study was to check synergistic effects of both plants (Barbadensis miller and Marsdenia condurango) against liver and cervical cancer. METHODOLOGY: Culturing of HeLa (cervical cancer cell line) and HepG2 (liver cancer cell line) cells, IC50 evaluation, viability assays (trypan blue, crystal violet), p53 ELISA and immunocytochemistry, MUSE analysis (count and viability), antioxidants (GSH, SOD, CAT), at the end RT-PCR was performed. RESULTS: IC50 evaluation was done of each plant individually and with combination for synergistic effects, IC50 with plants combination (synergism) was applied on further viability assays (trypan blue, crystal violet, MUSE analysis via count and viability kit) p53 ELISA and immunocytochemistry for evaluation of cellular apoptosis, antioxidants assays (GSH, SOD, CAT), and RT-PCR with proliferative and apoptotic markers along with internal control. CONCLUSION: According to current study it was observed that synergistic effect of these plants has more anticancer properties with minimum effective dose. It was also observed that extracts possess the ability to induce apoptosis, restrict proliferation and enhanced oxidative stress.

Anti-Proliferative and Apoptosis-Inducing Activity of Acacia Modesta and Opuntia Monocantha Extracts on HeLa Cells.

BACKGROUND: Cancer is one of the leading causes of death in the world. Numerous phytochemicals from plants have shown antineoplastic effects via programmed cell death (apoptosis). The aim of this study was to evaluate the effect of anti-proliferative and apoptosis-inducing activity of Acacia modesta and Opuntia monocantha against HeLa cells. METHODS: To estimate anti-proliferative activity of the plants against HeLa cells, ethanol solvent was used for the extraction. For the evaluation of anti-proliferative effects, MTT assay was performed with 100, 200, and 400 µg/mL dose. The antioxidant assays including glutathione reductase (GSH), superoxide dismutase (SOD) and catalase were performed. Moreover, enzyme linked immunosorbent assay (ELISA) was performed. Furthermore, immunocytometry P53 and flow cytometry were also carried out to assess the apoptosis in HeLa cell. RESULTS: MTT assay showed that the groups treated with Opuntia monocantha and Acacia modest have less level of toxicity as compared to untreated groups. Antioxidant assays confirmed that GSH, SPD and, catalase activities were quite decreased in treated groups as compared to untreated groups. Similarly, ELISA and apoptosis p53 have shown more pronounced apoptosis effect in treated groups as compared to untreated groups. CONCLUSION: Based on above findings, treatment of HeLa cells with these plant extracts induced apoptosis, restricts proliferation, and enhances the anti-oxidative index in post treated cells.
.

Compatibility analysis of bergapten with different pharmaceutical excipients used in nanostructured lipid carriers.

In pharmaceuticals sciences, Fourier-transform infrared spectroscopy (FTIR) is a very useful technique to measure the compatibility and interaction between ingredients, therefore in the current study, compatibility of bergapten with different excipients was analyzed via FTIR. Nanostructured lipid carriers (NLCs) are the second generation of lipid nanocarriers and very useful for the drug delivery systems. Nanoparticles (NPs) were prepared by a nanotemplate engineering technique and scanning of pure drug, individual ingredients and, physical mixtures of different ingredients was carried out. The characteristic peak of the carboxylic groups of bergapten is shifted from 3088.1 cm-1 to 3399.3 cm-1 due to formulation development and it confirmed that it was properly incorporated into the formulation. Other peaks of the drug were also present in formulation with minor shortening/broadening of peaks. The resulted peaks of IR spectra depicted that the ingredients used in the formulation had no considerable interaction and were found compatible with each other.

Development and evaluation of mucoadhesive buccal tablet containing metronidazole for the treatment of periodontitis and gingivitis.

The current study was designed to evaluate mucoadhesive buccal tablet containing metronidazole (MTZ) for local action aided by Hydroxypropylmethylcellulose K4M (HPMC) and Carbopol 940® (CP) as mucoadhesive polymers with other ingredients like sodium starch glycolate (SSG), polyvinyl pyrollidone K30 (PVP) as disintegrant and binders respectively. Formulations (F1-F8) were prepared by direct compression method and characterized for different physicochemical parameters. Results showed that the average weight and friability were within USP limits. Maximum mucoadhesive time was observed for F2 (14 hr) containing moderate amount of HPMC and CP used in the study. Up most mucoadhesive strength value was observed with F3 containing highest amount of HPMC used. Results indicated that high amount of HPMC was linked with the moderate to higher mucoadhesive strength and time. Maximum swelling index was observed in F7 (191.3%). Only F1-F3 showed complete in vitro MTZ release within 3 hr. Formulations containing PVP released MTZ incompletely over time while SSG released earlier. Formulation F1 was considered best in terms of MTZ release (100.5%) with diffusion based Korsmeyer-Peppas release kinetics. Therefore, MTZ exhibiting best physicochemical characters in mucoadhesive buccal tablet was found in F1 containing HPMC and CP in amounts of 37.5 mg and 25 mg, respectively, for local action.

RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.