Anti-Inflammatory Effects of Bioactive Compounds from Seaweeds, Bryozoans, Jellyfish, Shellfish and Peanut Worms.

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs.

Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. METHODS: In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes' annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. RESULTS: 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. CONCLUSIONS: We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.

Study protocol for a pilot randomized, double-blind, placebo-controlled trial to investigate the anti-inflammatory effects of Frondanol in adults with inflammatory bowel disease.

Introduction: Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a debilitating condition with a rising incidence globally over recent years. Frondanol, a widely available nutraceutical extract of the edible sea cucumber Cucumaria frondosa has been reported to possess potent anti-inflammatory effects, likely mediated by the inhibition of 5-lipoxygenase and 12-lipoxygenase pathways, whilst showing no signs of toxicity. The potent anti-inflammatory effects of Frondanol in a mouse model of IBD provide encouragement for investigating its effects in human IBD patients. Here we describe the study protocol of a pilot randomized, double-blinded, placebo-controlled trial of Frondanol in patients with mild to moderate IBD who are on standard therapy. Material and methods: One hundred patients will be randomized (1:1) to receive Frondanol or placebo as an adjunct to their standard therapy for the period of six months. Blood and stool samples will be obtained during routine visits at baseline, and after three months and six months of treatment, and tissue samples from colon biopsies will be obtained during clinically indicated colonoscopies at baseline and after six months of treatment. The levels of inflammatory markers will be compared in serum and tissue samples between patients treated with Frondanol and those treated with placebo, and findings will be correlated with clinical and histological parameters. Discussion: If proven beneficial, treatment with Frondanol may increase the likelihood of patients remaining in remission and potentially provide an effective, natural and safe addition/alternative for treatment-naive patients in the future.(Clinical trial registration number: NCT05194007).

Anti-Inflammatory Effects of Compounds from Echinoderms.

Chronic inflammation can extensively burden a healthcare system. Several synthetic anti-inflammatory drugs are currently available in clinical practice, but each has its own side effect profile. The planet is gifted with vast and diverse oceans, which provide a treasure of bioactive compounds, the chemical structures of which may provide valuable pharmaceutical agents. Marine organisms contain a variety of bioactive compounds, some of which have anti-inflammatory activity and have received considerable attention from the scientific community for the development of anti-inflammatory drugs. This review describes such bioactive compounds, as well as crude extracts (published during 2010-2022) from echinoderms: namely, sea cucumbers, sea urchins, and starfish. Moreover, we also include their chemical structures, evaluation models, and anti-inflammatory activities, including the molecular mechanism(s) of these compounds. This paper also highlights the potential applications of those marine-derived compounds in the pharmaceutical industry to develop leads for the clinical pipeline. In conclusion, this review can serve as a well-documented reference for the research progress on the development of potential anti-inflammatory drugs from echinoderms against various chronic inflammatory conditions.

Atorvastatin Improves Hepatic Lipid Metabolism and Protects Renal Damage in Adenine-Induced Chronic Kidney Disease in Sprague-Dawley Rats.

OBJECTIVE: Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders largely due to the dysregulation of lipoprotein metabolism which further aggravates the progression of kidney disease. The present study sought to determine the efficacy of atorvastatin treatment on hepatic lipid metabolism and renal tissue damage in CKD rats. METHODS: Serum, hepatic and faecal lipid contents and the expression and enzyme activity of molecules involved in cholesterol and triglyceride metabolism, along with kidney function, were determined in untreated adenine-induced CKD, atorvastatin-treated CKD (10 mg/kg/day oral for 24 days) and control rats. KEY FINDINGS: CKD resulted in metabolic dyslipidaemia, renal insufficiency, hepatic lipid accumulation, upregulation of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, acyl-CoA cholesterol acyltransferase-2 (ACAT2) and the downregulation of LDL receptor protein, VLDL receptor, hepatic lipase, lipoprotein lipase (LPL), lecithin-cholesterol acyltransferase (LCAT) and scavenger receptor class B type 1 (SR-B1). CKD also resulted in increased enzymatic activity of HMG-CoA reductase and ACAT2 together with decreased enzyme activity of lipase and LCAT. Atorvastatin therapy attenuated dyslipidaemia, renal insufficiency, reduced hepatic lipids, HMG-CoA reductase and ACAT2 protein abundance and raised LDL receptor and lipase protein expression. Atorvastatin therapy decreased the enzymatic activity of HMG-CoA reductase and increased enzymatic activity of lipase and LCAT. CONCLUSIONS: Atorvastatin improved hepatic tissue lipid metabolism and renal function in adenine-induced CKD rats.

Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats.

BACKGROUND: Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats. METHODS: Male SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits. RESULTS: The marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance. CONCLUSION: The results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.

Attenuation of Glucose-Induced Myoglobin Glycation and the Formation of Advanced Glycation End Products (AGEs) by (R)-α-Lipoic Acid In Vitro.

High-carbohydrate containing diets have become a precursor to glucose-mediated protein glycation which has been linked to an increase in diabetic and cardiovascular complications. The aim of the present study was to evaluate the protective effect of (R)-α-lipoic acid (ALA) against glucose-induced myoglobin glycation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The effect of ALA on myoglobin glycation was determined via the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The extent of glycation-induced myoglobin oxidation was measured via the levels of protein carbonyl and thiol. RESULTS: The results showed that the co-incubation of ALA (1, 2 and 4 mM) with myoglobin (1 mg/mL) and glucose (1 M) significantly decreased the levels of fructosamine, which is directly associated with the decrease in the formation of AGEs. Furthermore, ALA significantly reduced the release of free iron from myoglobin which is attributed to the protection of myoglobin from glucose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin from oxidative damage, as seen from the decreased protein carbonyls and increased protein thiols. CONCLUSION: The anti-glycation properties of ALA suggest that ALA supplementation may be beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. RESULTS: The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. CONCLUSION: These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

Chronic treatment of (R)-α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats.

(R)- α -lipoic acid (ALA), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes (T2D) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D. The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D.

Diuretic and antiurolithiatic activities of an ethanolic extract of Acorus calamus L. rhizome in experimental animal models.

Acorus calamus is a plant commonly used as a traditional herbal medicine and possesses the wide range of pharmacological applications. The present study investigated the diuretic and antiurolithiatic activities of an ethanolic extract of Acorus calamus L. (Family: Araceae) rhizome (EEAC). For diuretic activity, three doses of EEAC (250, 500 and 750 mg/kg) were studied, and measurement of the urinary volume and electrolytes (Na+ and K+) concentration were taken as evaluation parameters. On the other hand, ethylene glycol induced urolithiasis (0.75% v/v in drinking water for 28 days) was used to study the antiurolithiatic effect of EEAC at the oral dose of 750 mg/kg in male Wistar albino rats. CYSTONE (750 mg/kg, p.o.) was used as a standard reference drug in the present study. After completion of the 28-days respective treatments, the level of various urolithiatic promoters in the biological samples (urine, serum and kidney homogenate) and renal function were used as criteria for assessing the antiurolithiatic effect of EEAC. Results indicate that, the EEAC (750 mg/kg, p.o.) produced significant increase in urine volume (p < 0.001) and urinary excretion of Na+ and K+ electrolytes (p < 0.05) in a pattern comparable to that of furosemide. In ethylene glycol induced urolithiatic model, EEAC significantly (p < 0.05) decreased excretion and deposition of various urolithiatic promoters as compared to urolithiatic control in a pattern comparable to that of CYSTONE. The EEAC supplementation also prevents the impairment of renal functions. The antiurolithiatic mechanism is mediated possibly through diuretic and nephroprotective actions of the active compounds of rhizomes.

Evaluation of polyherbal formulation (SJT-HT-03) for antihypertensive activity in albino rats.

BACKGROUND: Hypertension is an incurable pathological condition and lifelong therapy is required. Long term use of conventional synthetic anti-hypertensive drugs is associated with a spectrum of toxic effects. However, therapeutic interventions using herbal drugs for hypertension have gained considerable attention worldwide. AIM: To evaluate the anti-hypertensive activity of polyherbal formulation (SJT-HT-03). MATERIALS AND METHODS: The polyherbal formulation (SJT-HT-03) comprises of leaves of Aegle marmelos L., fruits of Benincasa hispida Thunb., Garcinia indica Thouars, and flowers of Musa paradiasica L., Rosa indica L., Hibiscus rosa sinensis L. Selected plants as mentioned above were collected, dried and extracted with different solvents. Formulation SJT-HT-03 (250 mg/kg, p.o.), was evaluated using two kidney one clip (2K1C) model and deoxycorticosterone acetate (DOCA)-salt-induced hypertension model using the enalapril (10 mg/kg, p.o.) and hydrochlorothiazide (5 mg/kg, p.o.) as a reference standard drug in respective models. RESULTS: SJT-HT-03 significantly reduced (P < 0.001, one-way analysis of variance followed by Turkey's multiple comparison tests) systolic as well as diastolic blood pressure (BP) in 2K1C and DOCA-salt model. Further, SJT-HT-03 has shown a significant reduction (P < 0.01) in angiotensin converting enzyme (ACE) activity in serum, clipped kidney as well as in lungs in 2K1C model, whereas significant reduction (P < 0.05) in serum Na(+) and increase in serum K(+) level in DOCA model. CONCLUSION: Polyherbal formulation SJT-HT-03 possess significant anti-hypertensive activity by producing direct depressant effect on heart, inhibition of ACE, aldosterone antagonistic as well as diuretic effect and thereby act on multiple targets to achieve optimal effect.

MicroRNAs as newer therapeutic targets: A big hope from a tiny player.

MicroRNAs (miRNAs) are a novel group of universally present small noncoding endogenous RNAs that regulate gene expression and protein coding by base pairing with the 3' untranslated region (UTR) of target mRNAs. So they have been associated with several physiological processes and play an important role in the manifestation of diverse diseases. miRNAs expression is associated with the normal and diverse pathophysiological state including cardiac hypertrophy, neurodegenerative diseases, diabetes and its complication, and cancer because individual miRNAs are associated with the regulation of the expression of multiple target genes. Modulating the expression of a single miRNA can influence an entire gene network and thereby modify complex disease phenotypes. From recent studies, it has been confirmed that miRNA has a potential physiological role in various body systems. But in some specialized condition over expression of miRNA within the cytoplasm also leads to some pathological condition in the body. Here, we summarize the roles of miRNAs in various pathological conditions and consider the advantages and potential challenges of miRNA-based therapeutic approaches compared to conventional drug-based therapies.