Evaluation of photobiomodulation in the salivary production of patients with hyposalivation induced by antihypertensive drugs - A blind, randomized, controlled clinical trial.

BACKGROUND: Arterial hypertension is a systemic condition that affects about 35% of the world population. The drugs that are used for its control can produce hyposalivation. This work evaluated the effect of photobiomodulation on salivary flow rate, salivary pH, total protein concentration, and calcium concentration in individuals using antihypertensive medications. MATERIAL AND METHODS: 41 subjects were randomly allocated in one of two groups: control (placebo) and photobiomodulation. The subjects had their salivary glands (20 sites) irradiated with a laser emitting at 808 nm, 4J/site once a week for 4 weeks and had their salivary flow measured before and after the whole treatment. RESULTS: The intragroup analysis (before and after treatment) shows a significant difference for both non-stimulated and stimulated salivary flow in the photobiomodulation group (p = 0.0007 and p = 0.0001, respectively). Comparing the placebo with the photobiomodulation group, significant differences were found for both non-stimulated (p = 0.0441) and stimulated salivary flow (p = 0.0441) after the treatment. No significant differences were found in pH, total protein concentration, calcium concentration. CONCLUSION: Despite the usage of drugs that influence the nervous system and typically result in a reduction of saliva production, photobiomodulation demonstrated a remarkable ability to enhance saliva production by a significant 75%.

Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Study on material basis and anti-hypertensive metabolomics of Zhengan-Xifeng-Tang(ZXT): A comparison between ZXT decoction and granules.

High blood pressure is a serious human health problem and one of the leading risk factors for fatal complications in cardiovascular disease. The ZXT granules were prepared based on the Zhengan-Xifeng-Tang (ZXT) decoction. However, the therapeutic effects of ZXT granules on spontaneous hypertension and the metabolic pathways in which they may intervene are unclear. The aim of this study was to investigate the antihypertensive effect of ZXT granules on spontaneously hypertensive rats (SHR) and to analyze the metabolic pathway of intervention through chemical composition characterization, pharmacodynamics, and serum metabolomics analysis. After eight weeks of administration, serum and aortic arch samples were collected for biochemical, histopathology and serum metabolomics analysis to assess the effect of ZXT granules on SHR. The results showed that ZXT granules reduced aortic arch injury and blood pressure in SHR rats. Serum data from rats in each group was collected using LC-MS and 74 potential biomarkers were identified that showed significant differences between the model and control groups. Of these, 18 potential biomarkers were found to be deregulated after intervention with ZXT granules. These 18 potential differential metabolic markers are primarily involved in bile acid biosynthesis, arachidonic acid metabolism pathway, and fatty acid degradation. The results demonstrated that ZXT granules significantly affected blood lipids, aortic arch, and metabolic disorders in SHR rats. ZXT granules offer a new possibility for effective and convenient treatment of hypertensive patients.

Impacts of national volume-based drug procurement policy on the utilization and costs of antihypertensive drugs in a Chinese medicine hospital: an interrupted time series analysis of 5138 patients.

Objectives: The study aimed to estimate the effects of National Volume-based Drug Procurement (NVBP) policy on drug utilization and medical expenditures of hypertension patients in public medical institutions in mainland China. Methods: This study used patient-level data based on electronic health records retrieved from the hospital information system of Nanjing Hospital of Chinese Medicine. Data on patients with hypertension who received care at this institution between 2016 and 2021 was used for analysis. Segmented linear regression models incorporating Interrupted Time Series (ITS) analysis were adopted to examine the effects of NVBP policy on drug utilization and health expenditures of eligible patients. Drug utilization volume and health expenditures were the primary outcomes used to assess the policy effects, and were measured using the prescription proportion of each drug class and the overall per-encounter treatment costs. Results: After the implementation of NVBP policy, the volume of non-winning drugs decreased from 54.42% to 36.25% for outpatient care and from 35.62% to 15.65% for inpatient care. The ITS analysis showed that the volume of bid-winning drugs in outpatient and inpatient settings increased by 9.55% (p < 0.001) and 6.31% (p < 0.001), respectively. The volume changes in non-volume based purchased (non-VBP) drugs differed between outpatients and inpatients. The proportion of non-VBP drugs immediately increased by 5.34% (p = 0.002) overall, and showed an upward trend in the outpatient setting specially (p < 0.001) during the post-intervention period. However, no significant differences were observed in the proportion of non-VBP drugs in inpatient setting (p > 0.05) in term of level change (p > 0.05) or trend change (p > 0.05). The average per-visit expenditures of outpatients across all drug groups exhibited an upward trend (p < 0.05) post policy intervention. In addition, a similar increase in the overall costs for chemical drugs were observed in inpatient settings (coefficient = 2,599.54, p = 0.036), with no statistically significant differences in the regression slope and level (p = 0.814). Conclusion: The usage proportion of bid-winning drugs increased significantly post policy intervention, indicating greater use of bid-winning drugs and the corresponding substitution of non-winning hypertensive drugs. Drug expenditures for outpatients and health expenditures per visit for inpatients also exhibited an upward trend, suggesting the importance of enhanced drug use management in Traditional Chinese Medicine hospital settings.

Ifanosine: Olea europaea L. and Hyphaene thebaica L. combination, from traditional utilization to rational formulation: Preclinical and clinical efficacy on hypertensives patients.

ETHNOPHARMACOLOGICAL RELEVANCE: Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine). AIM OF THE STUDY: The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine. MATERIALS AND METHODS: In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days. RESULTS: Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects. CONCLUSION: This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies.

Exploring nature's hidden treasure: Unraveling the untapped phytochemical and pharmacological potentials of Clinopodium vulgare L. - A hidden gem in the Lamiaceae family.

Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative efforts to document historical records and preserve invaluable knowledge of medicinal plants. The Lamiaceae (Labiatae) family, renowned for its rich assortment of medicinal plants characterized by high concentrations of volatile oils, stands out in this regard. This review focuses on Clinopodium vulgare (C. vulgare) L., commonly known as wild basil or basil thyme, a significant species within the Lamiaceae family found across diverse global regions. C. vulgare boasts a storied history of application in treating various ailments, such as gastric ulcers, diabetes, and inflammation, dating back to ancient times. Rigorous research has substantiated its pharmacological properties, revealing its antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer, antihypertensive, and enzyme-inhibitory effects. This comprehensive review provides an insightful overview of the Lamiaceae family, elucidates the extraction methods employed to obtain medicinal compounds, explores the phytoconstituents present in C. vulgare, and systematically details its diverse pharmacological properties. Additionally, the review delves into considerations of toxicity. By synthesizing this wealth of information, this study opens avenues for the potential therapeutic applications of C. vulgare. The practical value of this research lies in its contribution to the understanding of medicinal plants, mainly focusing on the pharmacological potential of C. vulgare. This exploration enriches our knowledge of traditional medicine and paves the way for innovative therapeutic approaches, offering promising prospects for future drug development. As the demand for natural remedies continues to increase, this work provides a valuable resource for researchers, practitioners, and stakeholders in herbal medicine and pharmacology.

Extract of Chenopodium album lowers blood pressure in rats through endothelium-dependent and -independent vasorelaxation.

OBJECTIVES: To investigate the antihypertensive effect of crude extract of Chenopodium album (Ca.Cr), based on its medicinal use in hypertension. METHODS: Ca.Cr and its fractions were tested in-vivo in normotensive anesthetized rats for blood pressure-lowering effect. In-vitro experiments were performed on isolated rat aortae to explore the vascular mechanism(s). RESULTS: In normotensive anesthetized rats, Ca.Cr produced a dose-dependent (1-300mg/kg) fall (30%mmHg) in mean arterial pressure (MAP). Among the fractions, nHexane was the most potent (46% fall). In rat aortic rings precontracted with phenylephrine (PE), Ca.Cr and its fractions (except Ca.Aq) produced endothelium-dependent vasorelaxation, which was partially reversed with endothelium removal and by pretreating intact aortic rings with L-NAME (10µM) and atropine (1µM). This relaxation to Ca.Cr and fractions (nHexane, ethylacetate and chloroform) was also eliminated with indomethacin pretreatment, however, it unmasked a vasoconstriction effect with Ca.Cr only. Surprisingly, the aqueous fraction produced a calcium sensitive strong vasoconstriction instead of vasorelaxation. The crude extract and its fractions (except Ca.Aq) also antagonized vasoconstriction induced with high K+ (80mM), suggesting calcium antagonistic effect. The aqueous fraction produced mild vasorelaxation against high K+. This effect was further confirmed when pretreatment of the aortic rings with different concentrations of crude extract and fractions suppressed CaCl2 concentration response curves, similar to verapamil. In acute toxicity test, Ca.Cr extract was found safe up to 5g/kg body weight in mice. CONCLUSION: These findings suggest that crude extract and fractions of C. album produced vasorelaxant effect through muscarinic receptors linked-NO pathway, prostaglandin (endothelium-dependent) and calcium antagonism (endothelium-independent), which explains the blood pressure lowering effect of C. album in rats.

Anti-hypertensive and composition as well as pharmacokinetics and tissues distribution of active ingredients from Alpinia zerumbet.

Alpinia zerumbet is a food flavor additive and a traditional medicine herb around the world. Several studies have reported that A. zerumbet has excellent effects on a variety of cardiovascular diseases, but its potential hypertensive applications, and pharmacokinetic features of main active substances have not been fully investigated. The mechanism of anti-hypertension with ethyl acetate extracts of A. zerumbet fruits (AZEAE) was evaluated by L-NNA-induced hypertensive rats and L-NAME-injured human umbilical vein endothelial cells (HUVECs). Blood pressure, echocardiographic cardiac index and H&E staining were used to preliminary evaluate the antihypertensive effect of AZEAE, the levels of TNF-α, IL-6, and IL-1ß were evaluated by ELISA, and the proteins expression of IL-1ß, IL-18, AGTR1, VCAM, iNOS, EDN1 and eNOS were also evaluated. In addition, isolation, identification, and activity screening of bioactive compounds were carried ou. Next, pharmacokinetics and tissues distribution of dihydro-5,6-dehydrokavain (DDK) in vivo were measured, and preliminary absorption mechanism was conducted with Caco-2 cell monolayers. AZEAE remarkably enhanced the state of hypertensive rats. Twelve compounds were isolated and identified, and five compounds were isolated from this plant for the first time. The isolated compounds also exhibited good resistance against injury of HUVECs. Moreover, pharmacokinetics and Caco-2 cell monolayers demonstrated AZEAE had better absorption capacity than DDK, and DDK exhibited differences in tissues distribution and gender difference. This study was the first to assess the potential hypertensive applications of A. zerumbet in vivo and vitro, and the first direct and concise study of the in vivo behavior of DDK and AZEAE.

The Hypotensive and Vasodilatory Effects Observed in Rats Exposed to Chiranthodendron pentadactylon Larreat Flowers Can Be Attributed to Cyanidin 3-O-Glucoside.

Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3-O-glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.

Antihypertensive effect of the stem bark aqueous extract of Garcinia lucida Vesque (Clusiaceae) in L-NAME-treated rats: Contribution of endothelium-dependent and -independent vasorelaxation.

Garcinia lucida is used in Cameroonian folk medicine to handle a variety of ailments, including arterial hypertension. This study aimed at determining the phytochemical profile and the antihypertensive effect of the stem bark aqueous extract of G. lucida (AEGL). AEGL was subjected to LC-MS analysis, and its effect (75, 150, and 300 mg/kg/day; by gavage) was evaluated against Nω-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg)-induced hypertension in adult male Wistar rats for four consecutive weeks. Blood pressure and heart rate were monitored weekly using tail-cuff plethysmography. The vasorelaxant effect of cumulative concentrations (3-10-30-100-300 µg/mL) of AEGL was examined on endothelium-intact and denuded thoracic aorta rings which were precontracted with KCl (90 mM) or norepinephrine (NE; 10-5 M), and in the absence or presence of L-NAME (10-4 M), indomethacin (10-5 M), methylene blue (10-6 M), tetraethylammonium (TEA, 5 × 10-6 M), glibenclamide (10 × 10-6 M) or propranolol (5 × 10-6 M). The influence of AEGL on the response to NE, KCl, and CaCl2 was also investigated. Six compounds, including Garcinia biflavonoids GB1 and GB2, were identified. AEGL prevented the development of hypertension (p < 0.01 and p < 0.001) without affecting the heart rate. AEGL induced a concentration-dependent relaxation of aortic rings precontracted with NE (EC50 = 7.915 µg/mL) that was significantly inhibited by the removal of the endothelium, L-NAME, or methylene blue (p < 0.05-0.001). Indomethacin, propranolol, TEA, and glibenclamide did not affect AEGL-evoked vasorelaxation. Preincubation of aortic rings with AEGL reduced the magnitude of contraction elicited by CaCl2 but did not alter that of KCl or NE. AEGL possesses an antihypertensive effect that is mediated by both endothelium-dependent and endothelium-independent mechanisms. The activation of the NO/sGC/cGMP pathway accounts for the endothelium-dependent vasorelaxation. These pharmacological effects of AEGL could be attributed to the presence of the Garcinia biflavonoids GB1 and GB2.

Antihypertensive potential of the stem bark of Canarium schweinfurthii Engl. (Burseraceae) in wistar rats: UPLC-ESI-QToF-MS/MS-based prediction of antihypertensive phytochemicals.

Ethnopharmacological relevance: Canarium schweinfurthii, also called ''Elemierd'Afrique'', is used in Cameroonian folk medicine (bark decoction) to treat patients suffering from hypertension.Aim of the study: This study aimed at evaluating the antihypertensive activities of the stem bark of Canarium schweinfurthii and identifying potential compounds present in its extract that may support or oppose its ethnomedicinial use. Materials and methods: Stem bark extract of Canarium schweinfurthii was prepared by maceration using 70 % ethanol followed by redissolution in methanol and hyphenated. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) analysis for the detection and characterisation of secondary metabolites. Antihypertensive effects were assessed in Wistar rats after induction of hypertension with sodium chloride (NaCl) 18 % at a dose of 0.01mL/gbody weight once a day for four weeks.Hemodynamic parameters were measured weekly by anon-invasive method using the CODA system. Results: The ethanolic bark extract of C. schweinfurthii significantly inhibited the increase of blood pressure with a maximum of 23.18 % (systolic pressure, p < 0.0001), 24.77 % (diastolic pressure, p < 0.001) and 22.95 % (mean pressure, p < 0.0001) at a dose of 200 mg/kgbody weight at the 4th week, compared to agroup of Wistar rats that received only NaCl (negative control). Similarly, the extract significantly inhibited the increase in heart rate by 18.84 % (p < 0.001) at 200 mg/kgbody weight at week four. Hematological parameters did not differ significantly between the extract-treated and control groups. The UPLC-MS/MS spectrometric analysis provided evidence for the presence of several C30 terpenoids containing three or five oxygen atoms and exhibiting pentacyclic triterpenoid structures, as well as C29 terpenoids and related compounds containing nitrogen in addition to oxygen, using spectral matching, and in silico molecular formula and structure prediction. Additionally, two features were annotated with high-confidence as lignans, structurally closely related to hinokinin and dehydrocubebin through MS/MS-based in silico structure prediction using CSI: Finger ID in SIRIUS5. The lignans have been previously reported from stem bark of plants belonging to the Burseraceae family. Conclusion: The ethanolic stem bark extract of C. schweinfurthii demonstrated antihypertensive properties on the tested Wistar rats. These results support the ethnopharmacological use of C. schweinfurthii concoctions for the treatment of hypertension and suggest a protective effect against salt damage, hypothetically by the up regulation of antioxidative enzymes and/or lipids, mitigatings membrane peroxidation.

Antibacterial and Angiotensin I-Converting Enzyme (ACE) Inhibition Activities of Essential Oil from Java Cardamom (Amomum compactum) Fruit.

The essential oil has been reported to be one of the Angiotensin I-Converting Enzyme (ACE) inhibitor resources. Moreover, it has been proven against bacterial pathogens that cause infectious diseases. Amomum compactum is one source of essential oil, known as Javanese cardamom is a spice herb commonly used for flavouring food and traditional medicine in Indonesia. However, ACE inhibition activity of A. compactum has not been reported. The purposes of this study were to identify the main constituent of volatile compounds, inhibition activity toward bacteria, and antihypertension potency of A. compactum essential oils. Volatile compounds were investigated using Gas Chromatography-Mass Spectrometry (GC-MS). The antimicrobial activity was observed using the microdilution method toward Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. The antihypertension effect was studied using an ACE inhibition assay. The result showed that eucalyptol was a primary compound of A. compactum fruit either in Banjar (BJR) and Bogor (BGR) essential oils with the value of 62.22% and 66.23%, respectively. Both BJR and BGR are more active to inhibit gram-positive bacteria (B. subtilis) with MIC values of 1 mg/mL. Meanwhile, the BJR exhibited a higher inhibitory activity effect toward ACE compared to BGR with the value of IC50 64.86 ± 0.57 µg/mL. These findings suggest that A. compactum essential oil can be the potential to lead to the treatment of hypertension as an ACE inhibitor and antibacterial agent. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01080-x.

Bioactive molecules from terrestrial and seafood resources in hypertension treatment: focus on molecular mechanisms and targeted therapies.

Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin-angiotensin-aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.

Significant Advancement in Various Synthetic Strategies and Pharmacotherapy of Piperine Derivatives: A Review.

BACKGROUND: Piperine is a natural compound found in black pepper that has been traditionally used for various therapeutic purposes. In the ayurvedic system of medication there is a lot of evidence which shows that the piperine is widely used for different therapeutic purpose. In recent years, there has been an increasing interest in the pharmacological and therapeutic potential of piperine and its derivatives in modern medicine. In order to increase the bioavailability and therapeutic effectiveness of piperine and its analogs, researchers have been looking at various extraction methods and synthesis approaches. Many studies have been conducted in this area because of the promise of piperine as a natural substitute for synthetic medications. OBJECTIVES: The objective of this review article is to provide an up-to-date analysis of the literature on the synthesis of piperine analogs, including their extraction techniques and various biological activities such as antihypertensive, antidiabetic, insecticidal, antimicrobial, and antibiotic effects. Additionally, the review aims to discuss the potential of piperine in modern medicine, given its traditional use in various medicinal systems such as Ayurveda, Siddha, and Unani. The article also provides a comprehensive analysis of the plant from which piperine is derived. CONCLUSION: This review article provides a thorough examination of piperine and the source plant. The best extraction technique for the extraction of piperine and the synthesis of its analogs with various biological activities, including antihypertensive, antidiabetic, insecticidal, antibacterial, and antibiotic properties, are covered in the article. This review aims to provide an updated analysis of the literature on the synthesis of piperine analogs.

Statement on chronotherapy for the treatment of hypertension: consensus document from the Korean society of hypertension.

Nocturnal blood pressure (BP) has been shown to have a significant predictive value for cardiovascular disease. In some cases, it has a superior predictive value for future cardiovascular outcomes than daytime BP. As efficacy of BP medications wanes during nighttime and early morning, control of nocturnal hypertension and morning hypertension can be difficult. As such, chronotherapy, the dosing of BP medication in the evening, has been an ongoing topic of interest in the field of hypertension. Some studies have shown that chronotherapy is effective in reducing nocturnal BP, improving non dipping and rising patterns to dipping patterns, and improving cardiovascular prognosis. However, criticism and concerns have been raised regarding the design of these studies, such as the Hygia study, and the implausible clinical benefits in cardiovascular outcomes considering the degree of BP lowering from bedtime dosing. Studies have shown that there is no consistent evidence to suggest that routine administration of antihypertensive medications at bedtime can improve nocturnal BP and early morning BP control. However, in some cases of uncontrolled nocturnal hypertension and morning hypertension, such as in those with diabetes mellitus, chronic kidney disease, and obstructive sleep apnea, bedtime dosing has shown efficacy in reducing evening and early morning BP. The recently published the Treatment in Morning versus Evening (TIME) study failed to demonstrate benefit of bedtime dosing in reducing cardiovascular outcomes in patients with hypertension. With issues of the Hygia study and negative results from the TIME study, it is unclear at this time whether routine bedtime dosing is beneficial for reducing cardiovascular outcomes.

Hirsutine, an Emerging Natural Product with Promising Therapeutic Benefits: A Systematic Review.

Fruits and vegetables are used not only for nutritional purposes but also as therapeutics to treat various diseases and ailments. These food items are prominent sources of phytochemicals that exhibit chemopreventive and therapeutic effects against several diseases. Hirsutine (HSN) is a naturally occurring indole alkaloid found in various Uncaria species and has a multitude of therapeutic benefits. It is found in foodstuffs such as fish, seafood, meat, poultry, dairy, and some grain products among other things. In addition, it is present in fruits and vegetables including corn, cauliflower, mushrooms, potatoes, bamboo shoots, bananas, cantaloupe, and citrus fruits. The primary emphasis of this study is to summarize the pharmacological activities and the underlying mechanisms of HSN against different diseases, as well as the biopharmaceutical features. For this, data were collected (up to date as of 1 July 2023) from various reliable and authentic literature by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings indicated that HSN exerts several effects in various preclinical and pharmacological experimental systems. It exhibits anti-inflammatory, antiviral, anti-diabetic, and antioxidant activities with beneficial effects in neurological and cardiovascular diseases. Our findings also indicate that HSN exerts promising anticancer potentials via several molecular mechanisms, including apoptotic cell death, induction of oxidative stress, cytotoxic effect, anti-proliferative effect, genotoxic effect, and inhibition of cancer cell migration and invasion against various cancers such as lung, breast, and antitumor effects in human T-cell leukemia. Taken all together, findings from this study show that HSN can be a promising therapeutic agent to treat various diseases including cancer.

Sour Tamarind Is More Antihypertensive than the Sweeter One, as Evidenced by In Vivo Biochemical Indexes, Ligand-Protein Interactions, Multitarget Interactions, and Molecular Dynamic Simulation.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on an animal model's data verified by molecular docking, multitarget interactions, and dynamic simulation assays. GC-MS-characterized tamarind products were administered to cholesterol-induced hypertensive albino rat models. The two-week-intervened animals were dissected to collect their serum and organs and respectively subjected to analyses of their hypertension-linked markers and tissue architectures. The lead biometabolites of tamarinds interacted with eight target receptors in the molecular docking and dynamic simulation studies and with multitarget in the network pharmacological analyses. The results show that the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour tamarind extract compared to the sweet one, but the seed extracts had a smaller influence. Among the tamarind's biometabolites, ϒ-sitosterol was found to be the best ligand to interact with the guanylate cyclase receptor, displaying the best drug-likeliness with the highest binding energy, -9.3 Kcal. A multitargeted interaction-based degree algorithm and a phylogenetic tree of pathways showed that the NR3C1, REN, PPARG, and CYP11B1 hub genes were consistently modulated by ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 and 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be a prospective antihypertensive nutraceutical or supplement target affirmed through advanced preclinical and clinical studies.

Bitter Almond Albumin ACE-Inhibitory Peptides: Purification, Screening, and Characterization In Silico, Action Mechanisms, Antihypertensive Effect In Vivo, and Stability.

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 µmol·L-1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100-150 mg·kg bw-1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.

Screening potential hypertensive peptides using two consecutive bioassay-guided SPE fractionations and identification of an ACE inhibitory peptide, DHSTAVW (DW7), derived from pearl garlic protein hydrolysate.

The pearl garlic (Allium sativum L.) protein (PGP) was digested using pepsin, trypsin, α-chymotrypsin, thermolysin, and simulated gastrointestinal digestion. The α-chymotrypsin hydrolysate showed the highest angiotensin-I-converting enzyme inhibitory (ACEI) activity, with an IC50 value of 190.9 ± 11 µg/mL. A reversed-phase C18 solid-phase extraction (RP-SPE) cartridge was used for the first fractionation, and the S4 fraction from RP-SPE showed the most potent ACEI activity (IC50 =124.1 ± 11 3 µg/mL). The S4 fraction was further fractionated using a hydrophilic interaction liquid chromatography SPE (HILIC-SPE). The H4 fraction from HILIC-SPE showed the highest ACEI activity (IC50 =57.7 ± 3 µg/mL). Four ACEI peptides (DHSTAVW, KLAKVF, KLSTAASF, and KETPEAHVF) were identified from the H4 fraction using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and their biological activities were appraised in silico. Among the identified α-chymotryptic peptides, DHSTAVW (DW7), derived from I lectin partial protein, exhibited the most potent ACEI activity (IC50 value of 2.8 ± 0.1 µM). DW7 was resistant to simulated gastrointestinal digestion, and it was classified as a prodrug-type inhibitor according to the preincubation experiment. The inhibition kinetics indicated that DW7 was a competitive inhibitor, which was rationalized by the molecular docking simulation. The quantities of DW7 in 1 mg of hydrolysate, S4 fraction, and H4 fraction were quantified using LC-MS/MS to give 3.1 ± 0.1, 4.2 ± 0.1, and 13.2 ± 0.1 µg, respectively. The amount of DW7 was significantly increased by 4.2-fold compared with the hydrolysate, which suggested that this method is efficient for active peptide screening.

Study on material basis and anti-hypertensive metabolomics of different extraction methods of the Uncaria rhynchophylla Scrophularia Formula.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.