Anti-insomnia Effect of a Polyherbal Formulation on P-chlorophenyalanine Induced Experimental Animal Model.

Sleep is a dynamic and controlled set of physiological and behavioural practices during which the stabilisation and restoration processes of the body take place properly. Therefore, sleep disorders, especially chronic insomnia, can harm an individual's physical and mental health. However, the therapeutic alternatives are limited and possess severe side effects. Thus, in this study, we aimed to investigate the anti-insomnia effect of a polyherbal formulation (Sleep) (SLP) on p-chlorophenyalanine (PCPA) induced insomnia in rats. Intraperitoneal injection of PCPA induced the experimental condition, and the therapeutic effect of SLP was evaluated by studying the sleep pattern and expression of various neurotransmitters and receptors, along with neurotrophins. Moreover, insomnia-associated oxidative stress and inflammation were also studied. From the findings, we found that the SLP-supplemented animals improved their sleeping behaviour and that the major neurotransmitters, hormones, and receptors were maintained at an equilibrium level. Furthermore, the neurotrophin level was increased and pro-inflammatory cytokines were reduced. The evaluation of oxidative stress markers shows that the antioxidants were significantly boosted, and as a result, lipid peroxidation was prevented. The overall findings suggest that SLP can be used as an effective medication for the treatment of sleep disorders like insomnia as it triggers the major neurotransmitter system.

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.

Ameliorating effect of polyherbal formulation (Febrojith) on acute and chronic inflammatory model via inhibiting inflammation and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation is a complex biological response of the tissue to noxious stimuli, which causes several debilitating inflammatory disorders. Currently, various conventional medicines are available, but their consumption causes adverse effects, hence researchers focused on alternatives like medical herbs from natural sources, as one of the most promising sources of therapeutic agents for inflammation. Febrojith is a well-known traditional Ayurvedic formulation obtained from the treasures of Ayurveda with a unique blend of herbs that are used effectively in preventing and combating a broad spectrum of infections, fevers, and also enhancing immunity for many years. However, its anti-inflammatory, efficacy and underlying mechanism remained unexplored. AIM OF THE STUDY: In the present study, we investigated the chemical characterization and in vivo anti-inflammatory efficacy of Febrojith (FB) on acute and chronic inflammatory models via inhibiting inflammation and oxidative stress. MATERIALS AND METHODS: FB was analyzed for chemical characterization & its phytoconstituents by UV-Vis spectrum, FT-IR, and GC-MS analysis. The anti-inflammatory activity of FB was studied on carrageenan-induced acute and adjuvant-induced chronic experimental models. The inflammatory cytokines and mediators were measured using the ELISA & Colorimetry techniques. Histopathology and cytology of paw tissue and synovium were analyzed by H&E and Papanicolau's (PAP)-staining methods. RESULTS: 100 mg/kg bwt was found to be a potent dose from the carrageenan model and evaluated its effect in the adjuvant-induced chronic arthritic model. In the chronic model, 84% of edema inhibition was observed at the dose of 100 mg/kg bwt. Moreover, the supplementation of FB was shown to significantly (p ≤ 0.05) decrease the TBARS level and activity of myeloperoxidase in the paw tissue. In addition, adjuvant-induced production of various pro-inflammatory cytokines like TNF-α, IL-1ß, IL-6, PGE2, NO and COX-2 were suppressed in inflamed rats subjected to FB supplementation. It also revealed that FB supplementation significantly (p ≤ 0.05) reduced the haematological markers. From the histopathology and cytological analysis, we found a reduction in the edema formation, and infiltration of inflammatory cells after the supplementation of FB. CONCLUSION: In conclusion, FB might be used as an effective and potent drug against inflammation.

Anti-inflammatory and anti-COVID-19 effect of a novel polyherbal formulation (Imusil) via modulating oxidative stress, inflammatory mediators and cytokine storm.

In the current scenario, most countries are affected by COVID-19, a pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has a massive impact on human health. Previous studies showed that some traditionally used medicinal herbs and their combinations showed synergistic anti-viral and anti-inflammatory activity against SARS-CoV-2 type infections. Therefore, the goal of this study is to demonstrate the anti-viral and anti-inflammatory effects of a novel polyherbal formulation, hereinafter referred to as Imusil, on Vero E6 cell lines and Raw 264.7 murine macrophage cells respectively. The Imusil was subjected to identify its chemical characterisations such as UV-Visible spectrum profile, Fourier transform infrared spectroscopy (FT-IR) and gas chromatography-mass spectroscopic (GC-MS) analysis. FT-IR analysis of Imusil peak values with various functional compounds such as alcohol, esters, aliphatic and carboxylic acids. GC-MS analysis of compounds with totally 87 compounds major chemical compounds were identified, such as 3-(Octanoyloxy) propane-1,2-diyl bis(decanoate), Succinic acid, 2-methylhex-3-yl 2,2,2-trifluoroethyl ester, Neophytadiene, 3,5,9-Trioxa-4-phosphaheneicosan-1-aminium, 4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxododecyl)oxy]-, hydroxide, inner salt, 4-oxide, (R)-. The anti-viral activity of Imusil against SARS-CoV-2 was assessed using plaque reduction assay and anti-inflammatory study was conducted on lipopolysaccharide (LPS)-induced RAW 264.7 cells. The results obtained from the study reveal that Imusil significantly inhibited SARS-CoV-2 replication in Vero E6 cells and the production of inflammatory mediator's cyclooxygenase-2 and pro-inflammatory cytokines like tumour necrosis factor-α and interleukin- 6 were significantly reduced, along with thwarting the significant oxidative stress by preventing the expression of NOX-2 thereby inhibiting the reactive oxygen species formation. Hence, considering the current study as a novel strategy for mediating the COVID-19 associated aliments, inceptive scientific evidence of Imusil promises its potential therapeutic implications against COVID-19 and inflammatory conditions.

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.

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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Hepatoprotective effect of essential phospholipids enriched with virgin coconut oil (Phoscoliv) on paracetamol-induced liver toxicity.

The prevalence of liver disease is increasing year by year and it is recognized as a main health burden across the world. Nowadays, dietary nutraceuticals are found to be very effective in the prevention and treatment of liver diseases. The virgin coconut oil and phosphatidylcholine are found to have a wide range of therapeutic efficacy and the most important among them is its hepatoprotective activity. In the present study, we had evaluated the hepatoprotective effect of the novel formulation with the combination of these two which is named as Phoscoliv. For the study, adult Wistar rats were grouped into Normal control, Paracetamol-treated, and Paracetamol along with Phoscoliv-treated group. In order to evaluate the hepatoprotective effect of the drug, various parameters were analyzed. Data obtained from the study showed that Phoscoliv supplementation were found to significantly boost up the antioxidant status by enhancing the SOD, CAT, GPx, and GSH level and thereby inhibit the generation of ROS and also blocked lipid peroxidation, which was confirmed by the reduced level of TBARS. The release of pro-inflammatory cytokines was also decreased, which was eventually helped to maintain the normal architecture of the liver. Thus, from the overall result of this study reveals that Phoscoliv can be effectively used as a potent and safe hepatoprotective medicine. PRACTICAL APPLICATIONS: The over or unwanted usage of synthetic medicine is a serious problem because it can cause so many adverse health effects. Liver-related disorders are the major side effects of these drugs. Food habits of ancient people dictate that there is no other better medicine than a good food. So, treating a disease with a food or compounds derived from a food item will be more effective. Virgin coconut oil is a type of natural and organic oil, which has the capability of maintaining the body in a healthy state. Likewise, phosphatidylcholines are very important phospholipid nutrients necessary to keep the cells healthy. Both these have the potential to protect and prevent the liver damages. Therefore, the combination of these two can exhibit profound hepatoprotective activity.

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.

Anti-Ulcerative Effect of Curcumin-Galactomannoside Complex on Acetic Acid-Induced Experimental Model by Inhibiting Inflammation and Oxidative Stress.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.

Anti-inflammatory effect of synthesized indole-based chalcone (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one: an in vitro and in vivo studies.

Purpose: Chalcones are precursors of flavonoids with a wide range of pharmacological activities. This study evaluates the anti-inflammatory effect of indole based chalcone derivative (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9) on lipopolysaccharide (LPS) activated murine macrophages RAW264.7 cells and carrageenan-induced acute model in rats.Materials and methods: LPS-treated RAW264.7 cell lines and carrageenan-induced animal model were employed to evaluate the anti-inflammatory activity of IC9. The cell cytotoxicity studies were carried out by MTT assay. Reactive oxygen species (ROS) production and other inflammatory markers such as prostaglandin E2 (PGE2), nitric oxide (NO) as well as cyclooxygenase-2 (COX-2) activity were determined using ELISA. The RT-PCR was performed to determine mRNA expressions in the case of inducible nitric oxide synthase (iNOS), COX-2, Toll-like receptor-4 (TLR-4) and also nuclear translocation of NF-κB activity.Results: LPS-activated RAW264.7 cells showed an increased level of ROS generation and other inflammatory markers such as PGE2, NO level and COX-2 activity. Expression of iNOS, COX- 2 and TLR-4 mRNA expression were also up-regulated along with nuclear translocation of NF-κB. On IC9 supplementation, all the above parameters of LPS-activated cells were found to be reversed, resembling the control group. Moreover, IC9 significantly inhibited paw swelling and exhibited maximum inhibition of 78.45% at low dose of 7.5 mg/kg.bwt.Conclusions: The targeting anti-inflammatory efficacy and profound NF-κB sensitive transcriptional regulatory mechanism of IC9 accounts for its effective anti-inflammatory action.

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.