Resistance Training in Cardiovascular Diseases: A Review on Its Effectiveness in Controlling Risk Factors.

Cardiovascular Disease (CVD), a term encompassing various disorders affecting the heart and blood vessels, includes coronary artery disease (CAD). CAD is primarily due to the development of atherosclerotic plaques that disrupt blood flow, oxygenation, and nutrient delivery to the myocardium. Risk factors contributing to CAD progression include smoking, hypertension, diabetes mellitus (DM), dyslipidaemia, and obesity. While aerobic exercise (AE) has shown promising results in controlling CVD risk factors, the impact of resistance training (RT) has not been extensively investigated. This review aims to describe the effects of RT on CVD risk factors based on studies retrieved from PubMed and Google Scholar databases. Both isometric and isotonic RT have been found to decrease systolic blood pressure (SBP), diastolic blood pressure, or mean arterial pressure, with SBP showing a more significant reduction. Hypertensive patients engaging in RT alongside a calorie-restricted diet demonstrated significant improvements in blood pressure. RT is associated with increased nitric oxide bioavailability, sympathetic modulation, and enhanced endothelial function. In type-2 DM patients, 8-12 weeks of RT led to improvements in fasting blood glucose levels, insulin secretion, metabolic syndrome risk, and glucose transporter numbers. Combining AE with RT had a more significant impact in reducing insulin resistance and enhancing blood glucose compared to performing exercises separately. It also significantly decreased total cholesterol, triglycerides, and low-density lipoprotein levels while increasing high-density lipoprotein within 12 weeks of application. However, improvements are considered insignificant when lipid levels are already low to normal at baseline. The administration of RT resulted in weight loss and improved body mass index, with more pronounced effects seen when combining AE with RT and a calorie-restricted diet. Considering these results, the administration of RT, either alone or in combination with AE, proves beneficial in rehabilitating CAD patients by improving various risk factors.

Piper sarmentosum Roxb. Inhibits Angiotensin-Converting Enzyme Activity in Phorbol 12-Myristate-13-Acetate-Induced Endothelial Cells.

Angiotensin-converting enzyme (ACE) plays a crucial role in the pathogenesis of hypertension. Piper sarmentosum Roxb., an herb known for its antihypertensive effect, lacks a comprehensive understanding of the mechanism underlying its antihypertensive action. This study aimed to elucidate the antihypertensive mechanism of aqueous extract of P. sarmentosum leaves (AEPS) via its modulation of the ACE pathway in phorbol 12-myristate-13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs). HUVECs were divided into five groups: control, treatment with 200 µg/mL AEPS, induction 200 nM PMA, concomitant treatment with 200 nM PMA and 200 µg/mL AEPS, and treatment with 200 nM PMA and 0.06 µM captopril. Subsequently, ACE mRNA expression, protein level and activity, angiotensin II (Ang II) levels, and angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) mRNA expression in HUVECs were determined. AEPS successfully inhibited ACE mRNA expression, protein and activity, and angiotensin II levels in PMA-induced HUVECs. Additionally, AT1R expression was downregulated, whereas AT2R expression was upregulated. In conclusion, AEPS reduces the levels of ACE mRNA, protein and activity, Ang II, and AT1R expression in PMA-induced HUVECs. Thus, AEPS has the potential to be developed as an ACE inhibitor in the future.

Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring.

Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.

Evaluating the Potential of Plukenetia volubilis Linneo (Sacha Inchi) in Alleviating Cardiovascular Disease Risk Factors: A Mini Review.

Plukenetia volubilis Linneo or Sacha Inchi (SI), a traditional natural remedy indigenous to Peru and Brazil, has garnered global attention due to its exceptional nutritional composition. Its protective effects against various non-communicable diseases, notably cardiovascular disease (CVD), have become a subject of interest in recent research. This comprehensive review summarizes the existing evidence from 15 relevant articles concerning the impact of SI on common CVD risk factors, including dyslipidemia, obesity, diabetes, and hypertension. The relevant articles were derived from comprehensive searches on PubMed, Scopus, Google Scholar, and Web of Science using predefined criteria and keywords related to the topic. Overall, SI demonstrated positive effects in attenuating dyslipidemia, obesity, diabetes, and hypertension. The multifaceted mechanisms responsible for the protective effects of SI against these CVD risk factors are primarily attributed to its antioxidative and anti-inflammatory properties. While preclinical studies dominate the current scientific literature on SI, there are limited clinical trials to corroborate these findings. Therefore, future well-designed, large-scale randomized clinical trials are highly recommended to establish the efficacy of SI and determine its optimal dosage, potential drug and food interactions, and practical integration into preventive strategies and dietary interventions for the high-risk populations.

Nicotine Impairs the Anti-Contractile Function of Perivascular Adipose Tissue by Inhibiting the PPARγ-Adiponectin-AdipoR1 Axis.

Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ-adiponectin-adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ-adiponectin-adipoR1 axis.

Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review.

The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women's fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR "homeobox A10" OR PL OR HOX1 OR HOX1H OR HOX1.8) AND ("gene expression") AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.

Hyperandrogenism and Its Possible Effects on Endometrial Receptivity: A Review.

Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to hyperandrogenism or androgen excess, this condition can lead to pregnancy loss or infertility. Hyperandrogenism encompasses a wide range of clinical manifestations, including polycystic ovary syndrome (PCOS), idiopathic hirsutism, hirsutism and hyperandrogaenemia, non-classical congenital adrenal hyperplasia, hyperandrogenism, insulin resistance, acanthosis nigricans (HAIR-AN), ovarian or adrenal androgen-secreting neoplasms, Cushing's syndrome, and hyperprolactinaemia. Recurrent miscarriages have been shown to be closely related to elevated testosterone levels, which alter the endometrial milieu so that it is less favourable for embryo implantation. There are mechanisms for endometrial receptivity that are affected by excess androgen. The HOXA gene, aVß3 integrin, CDK signalling pathway, MECA-79, and MAGEA-11 were the genes and proteins affect endometrial receptivity in the presence of a hyperandrogenic state. In this review, we would like to explore the other manifestations of androgen excess focusing on causes other than PCOS and learn possible mechanisms of endometrial receptivity behind androgen excess leading to pregnancy loss or infertility.

Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease.

Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the Newcastle-Ottawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy.

Infertility and cortisol: a systematic review.

Introduction: Stress and infertility form a complex relationship. In line with this, various stress-related biological markers have been investigated in infertility. Methods: This systematic review was performed using PRISMA guidelines (i) to report whether cortisol is highly present in infertile patients compared to fertile control; (ii) to report whether there is any significant difference in the cortisol level in infertile subjects that conceive and those that didn't at the end of assisted reproduction treatments. Original articles involving human (male and female) as subjects were extracted from four electronic databases, including the list of references from the published papers. Sixteen original full-length articles involving male (4), female (11), and both genders (1) were included. Results: Findings from studies that compared the cortisol level between infertile and fertile subjects indicate that (i) Male: three studies reported elevated cortisol level in infertile patients and one found no significant difference; (ii) Female: four studies reported increased cortisol level in infertile subjects and three studies found no significant difference. Findings from studies that measured the cortisol level from infertile patients that conceived and those that didn't indicate that (i) Male: one study reported no significant difference; (ii) Female: one study reported elevated cortisol in infertile patients that conceived, whereas two studies reported increased cortisol in infertile patients that was unable to conceive. Five studies found no significant difference between the groups. Discussion: In the present review we only included the cortisol value that was measured prior to stimulation or IVF treatment or during natural or spontaneous cycles, despite this, there are still variations in the sampling period, assessment techniques and patients' characteristics. Hence, at present, we are still unable to conclude that cortisol is significantly elevated in infertile patients. We warrant future studies to standardize the time of biological sample collection and other limitations that were addressed in the review to negate the unwanted influencing factors.

Profiling of Differentially Expressed MicroRNAs in Human Umbilical Vein Endothelial Cells Exposed to Hyperglycemia via RNA Sequencing.

Hyperglycemia is the hallmark of diabetes mellitus that results in oxidative stress, apoptosis, and diabetic vascular endothelial dysfunction. An increasing number of microRNAs (miRNAs) have been found to be involved in the pathogenesis of diabetic vascular complications. However, there is a limited number of studies that characterize the miRNA profile of endothelial cells exposed to hyperglycemia. Therefore, this study aims to analyze the miRNA profile of human umbilical-vein endothelial cells (HUVECs) exposed to hyperglycemia. HUVECs were divided into two groups: the control (treated with 5.5 mM glucose) and hyperglycemia (treated with 33.3 mM glucose) groups. RNA sequencing identified 17 differentially expressed miRNAs between the groups (p < 0.05). Of these, 4 miRNAs were upregulated, and 13 miRNAs were downregulated. Two of the most differentially expressed miRNAs (novel miR-1133 and miR-1225) were successfully validated with stem-loop qPCR. Collectively, the findings show that there is a differential expression pattern of miRNAs in HUVEC following exposure to hyperglycemia. These 17 differentially expressed miRNAs are involved in regulating cellular functions and pathways related to oxidative stress and apoptosis that may contribute to diabetic vascular endothelial dysfunction. The findings provide new clues on the role of miRNAs in the development of diabetic vascular endothelial dysfunction, which could be useful in future targeted therapy.

Smoking and Unstable Plaque in Acute Coronary Syndrome: A Systematic Review of The Role of Matrix Metalloproteinases.

Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; I2 =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.

HOXA10 DNA Methylation Level in the Endometrium Women with Endometriosis: A Systematic Review.

Endometriosis is an inflammatory chronic systemic disease resulting in pelvic pain and infertility. However, despite a high prevalence of endometriosis, disease identification is still insufficient, and a high percentage of misdiagnosing was observed. Hence, a comprehensive study needs to be done to improve our understanding of the pathogenesis of endometriosis. Aberrant hypermethylation of HOXA10 has been reported to play a role in endometriosis. Thus, a comprehensive literature search was conducted to identify the DNA methylation level of HOXA10 among endometriosis patients across populations. The literature search was done using PubMed, Scopus, EBSCOhost, and Science Direct applying (HOXA10 OR "homeobox A10" OR "HOXA-10" OR HOX1) AND ("DNA methylation" OR methylation) AND (endometriosis OR endometrioma) as keywords. From 491 retrieved studies, five original articles investigating the DNA methylation level of HOXA10 from endometrium tissues among endometriosis women were included. All five included studies were classified as high-quality studies. High HOXA10 DNA methylation level was observed in the endometrium tissue of women with endometriosis in all the included studies. The secretory phase was identified as the best sampling time for HOXA10 DNA methylation study in endometriosis, and the most studied DNA methylation site is the promoter region of the HOXA10. However, more studies are needed to expose the HOXA10 mechanism in the pathogenesis of endometriosis.

Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review.

One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis. A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders.

Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model.

Reproductive and metabolic anomalies in polycystic ovary syndrome (PCOS) have been associated with the dysregulation of sex steroid receptors. Kelulut honey (KH) has been shown to be beneficial in PCOS-induced rats by regulating folliculogenesis and the oestrus cycle. However, no study has been conducted to evaluate KH's effect on sex steroid receptors in PCOS. Therefore, the current study examined the effects of KH, metformin, or clomiphene alone and in combination on the mRNA expression and protein distribution of androgen receptor (AR), oestrogen receptor α (ERα), oestrogen receptor ß (ERß), and progesterone receptor (PR) in PCOS-induced rats. The study used female Sprague-Dawley rats, which were treated orally with 1 mg/kg/day of letrozole for 21 days to develop PCOS. PCOS-induced rats were then divided and treated orally for 35 days with KH, metformin, clomiphene, KH + metformin, KH+ clomiphene and distilled water. In this study, we observed aberrant AR, ERα, ERß and PR expression in PCOS-induced rats compared with the normal control rats. The effects of KH treatment were comparable with clomiphene and metformin in normalizing the expression of AR, ERα, and ERß mRNA. However, KH, clomiphene and metformin did not affect PR mRNA expression and protein distribution. Hence, this study confirms the aberrant expression of sex steroid receptors in PCOS and demonstrates that KH treatment could normalise the sex steroid receptors profile. The findings provide a basis for future clinical trials to utilize KH as a regulator of sex steroid receptors in patients with PCOS.

Impact of offspring endothelial function from de novo hypertensive disorders during pregnancy: An evidence-based review.

De novo hypertensive disorders of pregnancy (HDP) which consist of gestational hypertension and preeclampsia affect maternal and offspring morbidity and mortality, and potentially increase the risk of cardiovascular disease in the offspring. It is well known that de novo HDP causes various maternal complications, including cardiovascular diseases, placental abruption and liver and kidney failure. However, there are studies suggesting that offspring of pregnancies complicated by de novo HDP have an increased risk of long-term cardiovascular disease. The endothelium is an important regulator of vascular function, and its dysfunction is highly associated with the development of cardiovascular diseases. Hence, this review aimed to systematically identify articles related to the effect of de novo HDP on the endothelial function of the offspring. A computerized database search was conducted on PubMed, Scopus, and Medline from 1976 until 2022. A total of 685 articles were obtained. We identified another three additional articles through review articles and Google Scholar. Altogether, we used 13 articles for data extraction. All studies reported that endothelial function was impaired in the offspring of de novo HDP. This is most likely attributed to impaired vasodilation, subclinical atherosclerosis formation, inflammation, and dysregulated epigenetic regulation of endothelial functions.

Kelulut Honey Ameliorates Oestrus Cycle, Hormonal Profiles, and Oxidative Stress in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Kelulut honey (KH) has been proven to have excellent antioxidative and anti-inflammatory properties with unique physicochemical characteristics. Therefore, we investigated the isolated and combined effects of KH, metformin, or clomiphene in alleviating oxidative stress and reproductive and metabolic abnormalities in polycystic ovary syndrome (PCOS). Female Sprague-Dawley (SD) rats were given 1 mg/kg/day of letrozole for 21 days to induce PCOS. PCOS rats were then divided into six treatment groups: untreated, metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were administered orally for 35 days. The physicochemical characteristics of KH were assessed through hydroxymethylfurfural, free acidity, diastase number, moisture content, sugar profile, metals, and mineral compounds. Additionally, we determined the semivolatile organic compounds present in KH through gas chromatography-mass spectrometry (GC/MS) analysis. KH and its combination with metformin or clomiphene were shown to improve the oestrus cycle, hormonal profile, and oxidative stress in PCOS rats. However, KH did not reduce the fasting blood glucose, insulin, and body weight gain in PCOS rats. These findings may provide a basis for future studies to discover the potential use of KH as a complementary treatment for women with PCOS.

Kelulut Honey Improves Folliculogenesis, Steroidogenic, and Aromatase Enzyme Profiles and Ovarian Histomorphology in Letrozole-Induced Polycystic Ovary Syndrome Rats.

Polycystic ovary syndrome (PCOS) has been linked to aberrant folliculogenesis and abnormalities in the aromatase enzyme (Cyp19a1) and the steroidogenic enzyme, 17-alpha-hydroxylase (Cyp17a1) expression. It has been demonstrated that Kelulut honey (KH) improves both female and male reproductive system anomalies in animal studies. Here, we examined the effects of isolated and combined KH, metformin, and clomiphene in improving folliculogenesis, aromatase, and steroidogenic enzyme profiles and ovarian histomorphology in letrozole-induced PCOS rats. Letrozole (1 mg/kg/day) was administered to female Sprague-Dawley (SD) rats for 21 days to induce PCOS. PCOS rats were subsequently divided into six experimental groups: untreated, treatment with metformin (500 mg/kg/day), clomiphene (2 mg/kg/day), KH (1 g/kg/day), combined KH (1 g/kg/day) and metformin (500 mg/kg/day), and combined KH (1 g/kg/day) and clomiphene (2 mg/kg/day). All treatments were given orally for 35 days. We found that KH was comparable with clomiphene and metformin in improving the expression of Cyp17a1 and Cyp19a1, apart from enhancing folliculogenesis both histologically and through the expression of folliculogenesis-related genes. Besides, the combination of KH with clomiphene was the most effective treatment in improving the ovarian histomorphology of PCOS rats. The effectiveness of KH in restoring altered folliculogenesis, steroidogenic, and aromatase enzyme profiles in PCOS warrants a future clinical trial to validate its therapeutic effect clinically.

Persicaria minor (Huds.) Opiz Prevents In Vitro Atherogenesis by Attenuating Tumor Necrosis Factor-α-Induced Monocyte Adhesion to Human Umbilical Vein Endothelial Cells.

Persicaria minor (Huds.) Opiz is an herb with anti-inflammatory, antioxidant, and anti-atherosclerosis effects. Nevertheless, the mechanism underlying its anti-atherosclerosis effect is poorly comprehended. This in vitro study assessed the protective effects of standardized aqueous extract of P. minor leaves (PM) on tumor necrosis factor-α (TNF-α)-induced monocyte adhesion to human umbilical vein endothelial cells (HUVEC), which is one of the pivotal early steps in atherogenesis. The results showed that PM decreased the mRNA and protein expression of cellular adhesion molecules, vascular adhesion molecule-1 and intercellular adhesion molecule-1, resulting in reduced adhesion of monocytes to HUVEC. Additionally, PM inhibited nuclear factor kappaB (NF-κB) activation as indicated by reduced NF-κB p65 levels in TNF-α-induced HUVEC. Overall, PM could prevent in vitro atherogenesis by inhibiting NF-κB activation and adhesion of monocytes to HUVEC. The effects of PM are probably mediated by its bioactive compound, quercetin-3-O-glucuronide. The findings may provide a rationale for the in vivo anti-atherosclerosis effect of PM, and support its potential use in atherosclerosis.

Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis.

Osteoarthritis (OA) is the most common type of arthritis and chronic joint disease, affecting more than 240 million people worldwide. Although there are numerous advances in using drugs in treating OA, the use of natural compounds has aroused much interest among researchers due to their safety margin. Recent discovery shows that natural compounds play an extensive role in the oxidative stress signaling pathway in treating OA. Thus, this review summarizes the commonly used natural compounds for treating OA focusing on the oxidative stress signaling pathway and its downstream mediators. Selected databases-such as Scopus, Web of Science, Nature, and PubMed-were used to search for potentially relevant articles. The search is limited to the last 15 years and the search was completed using the Boolean operator's guideline using the keywords of natural product AND oxidative stress AND osteoarthritis OR natural extract AND ROS AND degenerative arthritis OR natural plant AND free radicals AND degenerative joint disease. In total, 37 articles were selected for further review. Different downstream mechanisms of oxidative stress involved in the usage of natural compounds for OA treatment and anabolic and catabolic effects of natural compounds that exhibit chondroprotective effects have been discussed with the evidence of in vitro and in vivo trials in this review.