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.

Effects of Piper sarmentosum Roxb. on hypertension and diabetes mellitus: A systematic review and meta-analysis.

Hypertension and diabetes mellitus are among the most prevalent diseases affecting people from all walks of life. Medicinal herbs have garnered interest as potential agents for the prevention and treatment of diabetes mellitus and hypertension due to their multiple beneficial effects. Piper sarmentosum Roxb. (PS) is an edible medicinal plant that has been traditionally used in Asia for treating hypertension and diabetes mellitus. This review is aimed to provide comprehensive information from the literature on the effects of PS on hypertension and diabetes mellitus. A computerized database search was performed on Scopus, PubMed and Web of Science databases with the following set of keywords: Piper sarmentosum AND diabetes mellitus OR diabetic OR diabetes OR hyperglyc*emia OR blood glucose OR HbA1c OR glycated h*emoglobin OR h*emoglobin A1c OR hyperten* OR blood pressure. A total of 47 articles were screened and 14 articles published between the years 1998 until 2021 were included for data extraction, comprising of six articles on antihypertensive and eight articles on antidiabetic effects of PS. These studies consist of two in vitro studies and eleven in vivo animal studies. Meta-analysis of three studies on hypertension showed that PS versus no treatment significantly lowered the systolic blood pressure with mean difference (MD) -39.84 mmHg (95% confidence interval (CI) -45.05, -34.62; p < 0.01), diastolic blood pressure with MD -26.68 mmHg (95% CI -31.48, -21.88; p < 0.01), and mean arterial pressure with MD -30.56 mmHg (95% CI -34.49, -26.63; p < 0.01). Most of the studies revealed positive effects of PS against hypertension and diabetes mellitus, suggesting the potential of PS as a natural source of antidiabetic and antihypertensive agents.

Etlingera elatior Flower Aqueous Extract Protects against Oxidative Stress-Induced Nephropathy in a Rat Model of Type 2 Diabetes.

Diabetes mellitus (DM) is a known systemic disease with increasing global prevalence and multi-organ complications including diabetic nephropathy (DN). The trend of using medicinal plants in the management of DM is increasing exponentially. Etlingera elatior is a medicinal plant that contains chemicals and antioxidants that delay the oxidation process. However, available data focusing on its use on DN are inconsistent and scarce. This study aims to investigate the antidiabetic and nephroprotective effects of E. elatior flower aqueous extract (EEAE) in a type 2 DM rat (T2DR) model. The T2DR model was developed using a combination of a high-fat diet (HFD) and a low dose of streptozotocin (STZ) at 35 mg/kg. Thirty-two Sprague Dawley male rats were randomly divided into four groups (n = 8): (1) control (normal rat), (2) T2DR (untreated-type 2 diabetic rat), (3) Met (250 mg/kg metformin-treated T2DR), and (4) EEAE (1000 mg/kg EEAE-treated T2DR). All treatments were administered orally for 6 weeks. EEAE significantly reduced fasting blood glucose (FBG), microalbuminuria, serum creatinine, and serum blood urea nitrogen. EEAE also reduced malondialdehyde (MDA) and enhanced the levels of antioxidant markers-superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC). The inflammatory marker (interleukin (IL)-6) and fibrosis markers (transforming growth factor-beta (TGF-ß), and connective tissue growth factor (CTGF)) were significantly decreased in the EEAE-treated group. The T2DR group developed DN, which was characterized by segmental sclerosis of the glomeruli associated with focal tubular atrophy and interstitial fibrosis. Interestingly, the histology of kidney tissue in the EEAE group was preserved. This effect was similar to that of the control drug metformin. In summary, the antidiabetic and nephroprotective effects might be related to the antioxidant properties and anti-inflammatory effects of the EEAE. The antidiabetic activity could be due to the presence of the active compound cyanidin-3-O-glycosides, which is an anthocyanin antioxidant, that is present in the EEAE. E. elatior has the potential to be developed as a natural source of antioxidants that can be used for the prevention or even the treatment of DM. These findings could lead to future research into the therapeutic use of E. elatior in alleviating the progression of DM and thus preventing nephropathy.

The Anti-Viral and Anti-Inflammatory Properties of Edible Bird's Nest in Influenza and Coronavirus Infections: From Pre-Clinical to Potential Clinical Application.

Edible bird's nest (BN) is a Chinese traditional medicine with innumerable health benefits, including anti-viral, anti-inflammatory, neuroprotective, and immunomodulatory effects. A small number of studies have reported the anti-viral effects of EBN against influenza infections using in vitro and in vivo models, highlighting the importance of sialic acid and thymol derivatives in their therapeutic effects. At present, studies have reported that EBN suppresses the replicated virus from exiting the host cells, reduces the viral replication, endosomal trafficking of the virus, intracellular viral autophagy process, secretion of pro-inflammatory cytokines, reorient the actin cytoskeleton of the infected cells, and increase the lysosomal degradation of viral materials. In other models of disease, EBN attenuates oxidative stress-induced cellular apoptosis, enhances proliferation and activation of B-cells and their antibody secretion. Given the sum of its therapeutic actions, EBN appears to be a candidate that is worth further exploring for its protective effects against diseases transmitted through air droplets. At present, anti-viral drugs are employed as the first-line defense against respiratory viral infections, unless vaccines are available for the specific pathogens. In patients with severe symptoms due to exacerbated cytokine secretion, anti-inflammatory agents are applied. Treatment efficacy varies across the patients, and in times of a pandemic like COVID-19, many of the drugs are still at the experimental stage. In this review, we present a comprehensive overview of anti-viral and anti-inflammatory effects of EBN, chemical constituents from various EBN preparation techniques, and drugs currently used to treat influenza and novel coronavirus infections. We also aim to review the pathogenesis of influenza A and coronavirus, and the potential of EBN in their clinical application. We also describe the current literature in human consumption of EBN, known allergenic or contaminant presence, and the focus of future direction on how these can be addressed to further improve EBN for potential clinical application.

Modulation of Matrix Metalloproteinases by Plant-derived Products.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent metalloendopeptidases that are responsible for the degradation, repair, and remodeling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases, such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic, and food industries. This review summarises the current knowledge of plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signaling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviors, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

Antioxidative and anti-inflammatory activities of Polygonum minus: a review of literature.

Inflammation and oxidative stress are involved in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension and ischemic heart disease. Natural products play an important role as nutritional supplements with potential health benefits in cardiovascular diseases. Polygonum minus (PM) is an aromatic plant that is widely used as a flavoring agent in cooking and has been recognized as a plant with various medicinal properties including antioxidative and anti-inflammatory actions. Phytoconstituents found in PM such as phenolic and flavonoid compounds contribute to the plant's antioxidative and anti-inflammatory effects. We conducted this review to systematically identify articles related to the antioxidative and anti-inflammatory activities of PM. A computerized database search was conducted on Ovid MEDLINE, PubMed, Scopus, and ACS publication, from 1946 until May 2020, and the following keywords were used: 'Kesum OR Polygonum minus OR Persicaria minor' AND 'inflammat* OR oxida* OR antioxida*'. A total of 125 articles were obtained. Another eight additional articles were identified through Google Scholar and review articles. Altogether, 17 articles were used for data extraction, comprising 16 articles on antioxidant and one article on anti-inflammatory activity of PM. These studies consist of 14 in vitro studies, one in vivo animal study, one combined in vitro and in vivo study and one combined in vitro and ex vivo study. All the studies reported that PM exhibits antioxidative and anti-inflammatory activities which are most likely attributed to its high phenolic and flavonoid content.

Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells.

BACKGROUND: Aqueous extract of Piper sarmentosum (AEPS) is known to possess antioxidant and anti-atherosclerotic activities but the mechanism responsible for it remains unclear. In early part of atherosclerosis, nuclear factor-kappa B (NF-κB) induces the expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and E-selectin. NADPH oxidase 4 (Nox4) is the predominant source of superoxide in the endothelial cells whereas superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase (GPx) are the antioxidant enzymes responsible for inactivating reactive oxygen species. The present study aimed to investigate the effects of AEPS on the gene expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx in cultured human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were divided into four groups:- control; treatment with 180 µM hydrogen peroxide (H2O2); treatment with 150 µg/mL AEPS and concomitant treatment with AEPS and H2O2 for 24 hours. Total RNA was extracted from all the groups of HUVEC using TRI reagent. Subsequently, qPCR was carried out to determine the mRNA expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx. The specificity of the reactions was verified using melting curve analysis and agarose gel electrophoresis. RESULTS: When stimulated with H2O2, HUVECs expressed higher level of ICAM-1 (1.3-fold) and Nox4 (1.2-fold) mRNA expression. However, AEPS treatment led to a reduction in the mRNA expression of ICAM-1 (p < 0.01) and Nox4 (p < 0.05) in the H2O2-induced HUVECs. AEPS also upregulated the mRNA expression of SOD1 (p < 0.05), CAT (p < 0.01) and GPx (p < 0.05) in oxidative stress-induced HUVECs. There was no significant change in the mRNA expression of VCAM-1 and E-selectin. CONCLUSION: The expressional suppression of ICAM-1 and Nox4 and induction of antioxidant enzymes might be an important component of the vascular protective effect of AEPS.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

OBJECTIVE: Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). METHODS: HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. RESULTS: Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. CONCLUSION: Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells

OBJECTIVE: Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were divided into four groups: control, treatment with 180 ìM hydrogen peroxide (H2O2), treatment with 150 ìg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H2O2 for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. RESULTS: Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. CONCLUSION: Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.