Immunomodulatory Effect of a Polyherbal Formulation (Imusil) on Cyclophosphamide Induced Experimental Animal Model.

OBJECTIVE: In the present study, we investigated the immunomodulatory effect of a polyherbal formulation referred to as Imusil (IM) on cyclophosphamide (CP) induced immunosuppression model. METHODS: CP induced experimental animal model was used for evaluating the immunomodulatory effect of IM. For the study, animals were divided into four groups. Group I is served as the normal control, group II is treated only with CP, group III is treated with the standard drug, levamisole and group IV is treated with IM. The experimental duration was 30 days. At the end of the study, we had evaluated various parameters such as immune organ index, liver marker enzymes, antioxidants, haematological analysis, Th1/Th2 cytokine balance and humoral immune responses were examined using ELISA kits, T-lymphocyte subsets by flow cytometry, and histopathological analysis of the liver, spleen and thymus by H&E staining. RESULTS: The results obtained from the study revealed that the treatment of immunosuppressed animals with IM significantly (p<0.05) reversed the immune response in a positive manner. Treatment with IM properly shields the immune organs and triggers the cell-mediated and humoral immune responses accordingly. Thus, no significant changes were observed in the haematological parameters. Moreover, IM supplementation helps to boost up the antioxidant activity, thereby preventing oxidative stress-mediated damage, and also protects the liver from the toxicity induced by CP. CONCLUSION: The results suggest that IM has the ability to counteract the immunosuppressive effect of chemotherapeutic drugs by stimulating the immune system, along with its potent antioxidant and hepatoprotective properties.

Anti-inflammatory effect of Kaba Sura Kudineer (AYUSH approved COVID-19 drug)-A Siddha poly-herbal formulation against lipopolysaccharide induced inflammatory response in RAW-264.7 macrophages cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal importance and potential activity of Siddha herbal formulations have proved over several centuries against a wide range of causative agents as Influenza, Dengue, Chikungunya, and Tuberculosis. The traditional medicine system of Siddha is a valuable therapeutic approach for treating viral respiratory infections like Coronavirus disease 2019 (COVID-19) and can be effectively employed to target the host response and preventive care to boost the immune system. Kaba Sura Kudineer (KSK), an official polyherbal formulation has been used in Siddha traditional medicine for centuries. However, the role of KSK in regulating inflammation and the underlying molecular mechanisms has remained elusive. AIM OF THE STUDY: The goal of this study was to evaluate the anti-inflammatory effect of KSK using lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophage cells. MATERIALS AND METHODS: Raw 264.7 murine macrophage cells were used for this study. The Inflammatory mediators and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The NF-κB nulcear translocation and protein expression of iNOS, COX-2 was analyzed with westernblot. RESULTS: KSK supplementation decreased LPS mediated TLR-4 production and secretion of pro-inflammatory mediators and cytokines including IL-6, TNF-α, COX-2 and PGE-2. Moreover, it inhibited the production of nitric oxide (NO) and thereby inhibited the expression of iNOS in the cell. The Western blot analysis further confirmed that KSK strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB and hereby suppressed nuclear translocation of NF-κB. The protein expression of iNOS, COX-2 was significantly decreased with the presence of KSK treatment. Results suggested that KSK manipulates its anti-inflammatory effects mainly through blocking the TLR mediated NF-κB signal transduction pathways. CONCLUSIONS: Together, this study has proven that KSK could be a potential therapeutic drug for alleviating excessive inflammation in many inflammation-associated diseases like COVID-19.

Grazing behaviour of tropical calanoid copepods and its effect on phytoplankton community structure.

The Netravathi estuary is a micro- to mesotidal, tropical, shallow estuary with an abundant density of phytoplankton. The impact of the zooplankton grazing rate and the selected environmental variables on the phytoplankton community structure was studied seasonally from 2017 to 2019. Microplanktons of centric diatoms such as Skeletonema costatum and Cosinodiscus radiatus dominated during monsoon seasons, whereas dinoflagellates such as Peridinium sp. and Ceratium furca were observed in high numbers at the estuary during non-monsoon seasons. Water temperature showed a strong association with grazing rates of microzooplankton (r = 0.910). Canonical correspondence analysis studies established an intensification in grazing rate during non-monsoon seasons by calanoid copepods which in turn occasioned the reduction of microplanktons belonging to diatoms. Moreover, during monsoon seasons, diminution in grazing rates of calanoid copepods coupled with the presence of micro larvae as a secondary consumer of zooplankton resulted in the proliferation of centric diatoms. The grazing behaviour of microzooplankton affected the phytoplankton species diversity of the estuary in a negative manner (D = 0.29 in 2017 Pre-M, D = 0.76 in 2019 Pre-M). Selective grazing behaviour of calanoid copepods concerning temperature alteration exerted a strong influence in determining the phytoplankton community structure of the estuary to a great extent.

Curcumin-Galactomannoside Complex inhibits the Proliferation of Human Cervical Cancer Cells: Possible Role in Cell Cycle Arrest and Apoptosis.

BACKGROUND: Cervical cancer is the most common cancer and has the highest morbidity rate of gynaecological malignancies in women worldwide. So, the development of effective anti-cancer agents to treat this condition is vital. Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade, free-curcuminoids (curcumin-galactomannoside complex; CGM) on cervical cancer cells (HeLa) of human origin. In this study, we examined the anticancer potential of CGM as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell. METHODS: Determination of anti-proliferative and apoptosis validation of CGM on HeLa cells was performed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide and annexin-V-fluorescein isothiocyanate assays. Measurement of Reactive Oxygen Species (ROS) production, Caspase activities and protein expression experiments were performed to investigate the potential mechanisms of action in the apoptotic process. RESULTS: The cytotoxic assays revealed that the CGM showed inhibition of cell survival and exhibited high cytotoxic activity against HeLa cells at 25 µg/mL. Further studies on morphological changes were done in CGM-treated cervical cancer cells contributing to apoptosis. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that CGM induced apoptosis in HeLa cell lines at 25 µg/mL. By the supplementation of CGM showed an increase in Bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. CONCLUSION: The evidence obtained from this study suggests that CGM is a potent and promising natural formulation against cervical cancer cells via induction of apoptosis through ROS mediated mitochondrial damage in HeLa cells. Hence, CGM could be further explored as a potential lead in treating cancer.
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Biochemical and immunological aspects of COVID-19 infection and therapeutical intervention of oral low dose cytokine therapy: a systematic review.

The novel coronavirus (SARS-CoV-2) pandemic has now spread to all corners of the world. It causes severe respiratory syndromes which is one of the leading causes of death. Evidence shows that the novel SARS-CoV-2 has close similarities with other coronaviruses, SARS and MERS. So, SARS-CoV-2 might use the similar mechanisms of these viruses to attack the host cells. The severity of COVID-19 is associated with various factors, one of the major reasons is immune dysregulation or immune suppression. Immunity plays a significant role in maintaining the body in a healthy condition. In order to induce a timely immune response against the invaded pathogens, both innate and adaptive immunity must be in an active state. During the viral infection, there will be an excessive generation of pro-inflammatory cytokines known as cytokine storm and also, the antiviral agents in the body gets inhibited or inactivated through viral mechanisms. Thus, this might be the reason for the transition from mild symptoms to more severe medical conditions which leads to an immediate need for the invention of a new medicine.This review aims to show the host-viral interaction along with immune response, antiviral mechanism and effectiveness of oral low dose cytokines against the virus as a therapeutic approach.

Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers.

Fresh oyster white translucent sap obtained from the tender unopened inflorescence of coconut trees (Cocos nucifera) is identified to have great health benefits. Drug induced Nephrotoxicity is one of the major causes of renal damage in present generation. As a therapeutic agent, gentamicin imparts direct toxicity to kidney, resulting in acute tubular necrosis, glomerular and tubulointerstitial injury, haemodynamically mediated damage and obstructive nephropathy.There exists an increasing demand for safe and natural agents for the treatment and/or preventionofchronic nephrotoxicity and pathogenesis of kidney diseases. Our study shows the nephro protective/curing effect of a novel powder formulation of micronutrient enriched, unfermented coconut flower sap (CSP). The study was performed on adult male Wistar rats. The animals were grouped into three and treated separately with vehicle, gentamicin and gentamicin+CSP for 16days. Initially, gentamicin treatment significantly (p<0.05)reduced thelevels of antioxidant enzymes (SOD, CAT, GPx) and GSH and increased (p<0.05) the levels of creatinine, uric acid, urea, inflammatory markers (nitrite, IL-6, TNF- α, iNOS) and lipid peroxidation. Supplementation of coconut flower sap powder showed significant (p<0.05) reversal of all these biochemical parameters indicating an effective inhibition of the pathogenesis of nephrotoxicity and kidney disease.

Proliferation of dinoflagellates in Kochi estuary, Kerala.

Phytoplankton community structure and dynamics of Kochi estuary (bar mouth) have been studied seasonally. Three seasonal samplings namely pre-monsoon, monsoon and post-monsoon were made, and a wide variation was observed in phytoplankton community with respect to nutrients and other physicochemical parameters. Contrary to other seasons, dinoflagellate cell density increased during pre-monsoon season though species diversity was less pronounced (D > 0.15). Peridinium oceanicum was the dominant dinoflagellate during pre-monsoon season. Significant fluctuation in three principal nutrients namely total nitrogen, total phosphorous and silicate were observed during pre-monsoon (TP < 1.8 micromol l(-1), TN > 40 micromol l(-1) and SiO4 < 20 micromol l(-1)) season as compared to monsoon season (TP > 3.20 micromol l(-1), TN < 20 micromol l(-1) and SiO4 > 27 micromol l(-1)). Salinity values were also found to be high during pre-monsoon ( > 25 psu). Study suggests that variation in salinity and nutrient concentration during transition of seasons could result in succession of species, thereby causing change in phytoplankton community structure. High salinity and nitrogen values along with low values of silicate and phosphorous resulted in proliferation of dinoflagellates during pre-monsoon season.