Chlorogenic acid rich in coffee pulp extract suppresses inflammatory status by inhibiting the p38, MAPK, and NF-κB pathways.

Coffee pulp (CP) is a coffee byproduct that contains various active ingredients, namely, chlorogenic acid (CGA) and caffeine. These active compounds show several benefits, including antihyperlipidemia, antioxidants, and anti-inflammation. However, the anti-inflammatory properties of Coffea pulp extract (CPE) are unknown. This work determined the impact of CPE on lipopolysaccharide (LPS)-activated murine macrophage cells and the molecular mechanism behind this action. RAW 264.7 cells were exposed to varying doses of CPE with or without LPS. Inflammatory markers and their mechanism were studied. CPE therapy has been shown to suppress the synthesis of inflammatory cytokines and mediators, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1ß, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), as well as prostaglandin E2 (PGE2). Finally, CPE inactivated the nuclear factor-kappa B (NF-κB) and MAPK signaling pathways. Consequently, CPE might be used as a nutraceutical to treat inflammation and its related disorders.

The relationships between stress, stress-coping behaviors, and suicidal risk among Thais who had become unemployed due to the COVID-19 pandemic: A cross-sectional study.

Background: The COVID-19 pandemic has resulted in severe mental health problems worldwide. Thus, in addition to the high number of people who have died from infection with complications, some have committed suicide. Objective: This study aimed to determine the relationships between stress, stress-coping behaviors, and suicidal risk among those who had become unemployed in Thailand due to the COVID-19 pandemic. Methods: This study had a cross-sectional correlational design and included 447 unemployed Thais at least 18 years of age who had become unemployed due to the COVID-19 pandemic. The participants were selected through multistage sampling. A self-administered questionnaire was used for data collection. The data were then analyzed using frequency, percentage, and Spearman's correlation coefficient. Results: Most participants had moderate-level stress (73.16%) and stress-coping behaviors (71.81%). Almost all the participants had no suicidal risk (76.73%). The stress level and overall stress-coping behavior were positively correlated with suicidal risk (r = 0.305, p <0.01 and r = 0.352, p <0.01, respectively). Conclusion: Stress and stress-coping behaviors were associated with suicidal risk among Thais who had become unemployed due to the COVID-19 pandemic. Hence, nurses must screen patients with psychological problems, especially those who have become unemployed due to the COVID-19 pandemic, for suicide risk. Developing interventions to reduce such patients' stress and promote appropriate stress-coping behaviors is essential.

Characterization of Metabolites in Plasma, Urine and Feces of Healthy Participants after Taking Brahmi Essence for Twelve Weeks Using LC-ESI-QTOF-MS Metabolomic Approach.

Brahmi essence, developed from Bacopa monnieri (L.) Wettst. standardized extract and mulberry juice, was proven to improve the memory speed of healthy participants aged 55-80 years old, following a 12-week dietary program. However, the metabolites have not yet been reported. Our objective was to characterize the altered metabolites in the plasma, urine, and feces of healthy volunteers after consumption of Brahmi essence for 12 weeks, using the LC-MS metabolomics approach. The altered metabolites were selected from OPLS-DA S-plots; 15 metabolites in the plasma, 7 in the urine, and 17 in the feces samples were tentatively identified by comparison with an online database and literature. The metabolites in the plasma samples were in the classes of amino acids, acylcarnitine, and phospholipids. Benzeneactamide-4-O-sulphate and 3-hydroxyhippuric acid were found in urine samples. The metabolites in the class of amino acids, together with jujubogenin and pseudojujubogenin, were identified in the fecal samples. The aminoacyl-tRNA, aromatic amino acids, and branched-chain amino acid biosynthetic pathways were mainly related to the identified metabolites in all three samples. It could be implied that those metabolites and their pathways might be linked with the effect of Brahmi essence on memory speed.

Extract of Aquilaria crassna leaves and mangiferin are vasodilators while showing no cytotoxicity.

The leaves of Aquilaria spp. promote "physiological balance", and are "cardiotonic and provide blood nourishment". In Asia, these leaves are increasingly consumed as tea and claimed to provide benefits to cardiovascular function, albeit without any scientific proof. Therefore, this study sought to evaluate the action of Aquilaria crassna leaf aqueous extract (AE) on vascular function and vascular smooth muscle cytotoxicity. AE and a main constituent, mangiferin were investigated for their vasorelaxation of rat mesenteric arteries and aortae in vitro. Acute cytotoxicity of AE (0.1-1000 µg/ml) and mangiferin (0.1-100 µM) on rat enzymatically isolated vascular smooth muscle cells was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. AE dilated rat mesenteric arteries (EC50∼107 µg/ml, Emax∼95%) more than aorta (EC50∼265 µg/ml, Emax∼76%, p < 0.05). AE-induced vasodilation in mesenteric artery was reduced by endothelial removal (EC50∼202 µg/ml, p < 0.05), incubation with endothelial nitric oxide synthase (eNOS) (100 µM, L-NAME) (EC50∼309 µg/ml, p < 0.05), and partly reduced by L-type Ca2+ channel blockade at higher concentrations. Likewise, mangiferin (1-100 µM) dilated the mesenteric artery more potently than the aorta. However, its maximum relaxation was less than with AE (41% in the mesenteric artery and <10% in the aorta). Isolated vascular smooth muscle cells incubated in AE or mangiferin for 1 h showed no cytotoxicity. Thus, AE is a vasorelaxant while being free of acute cytotoxicity towards vascular smooth muscle, thus potentially ameliorating human vascular dysfunction.

Vasodilatory Effects and Mechanisms of Action of Bacopa monnieri Active Compounds on Rat Mesenteric Arteries.

B. monnieri extract (BME) is an abundant source of bioactive compounds, including saponins and flavonoids known to produce vasodilation. However, it is unclear which components are the more effective vasodilators. The aim of this research was to investigate the vasorelaxant effects and mechanisms of action of saponins and flavonoids on rat isolated mesenteric arteries using the organ bath technique. The vasorelaxant mechanisms, including endothelial nitric oxide synthase (eNOS) pathway and calcium flux were examined. Saponins (bacoside A and bacopaside I), and flavonoids (luteolin and apigenin) at 0.1-100 µM caused vasorelaxation in a concentration-dependent manner. Luteolin and apigenin produced vasorelaxation in endothelial intact vessels with more efficacy (Emax 99.4 ± 0.7 and 95.3 ± 2.6%) and potency (EC50 4.35 ± 1.31 and 8.93 ± 3.33 µM) than bacoside A and bacopaside I (Emax 83.6 ± 2.9 and 79.9 ± 8.2%; EC50 10.8 ± 5.9 and 14.6 ± 5.4 µM). Pretreatment of endothelial intact rings, with L-NAME (100 µM); an eNOS inhibitor, or removal of the endothelium reduced the relaxant effects of all compounds. In K+-depolarised vessels suspended in Ca2+-free solution, these active compounds inhibited CaCl2-induced contraction in endothelial denuded arterial rings. Moreover, the active compounds attenuated transient contractions induced by 10 µM phenylephrine in Ca2+-free medium containing EGTA (1 mM). Thus, relaxant effects occurred in both endothelial intact and denuded vessels which signify actions through both endothelium and vascular smooth muscle cells. In conclusion, the flavonoids have about twice the potency of saponins as vasodilators. However, in the BME, there is ~20 × the amount of vaso-reactive saponins and thus are more effective.

Bacopa monnieri extract increases rat coronary flow and protects against myocardial ischemia/reperfusion injury.

BACKGROUND: This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. METHODS: In normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 µg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca2+-currents (ICa, L) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion. RESULTS: In normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 µg/ml) and 216 ± 21% (100 µg/ml), compared to control (5 ± 3%) (n = 8-10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 µg/ml), 82 ± 10% (100 µg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 µg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 µg/ml) reduced ICa, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50-1000 µg/ml) B. monnieri. CONCLUSIONS: B. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.

Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure.

Bacopa monnieri (L.) Wettst. (Brahmi in India and Thailand) is an ayurvedic dementia treatment, but its effect on cerebral blood flow (CBF) is still unknown. We sought to test its chronic and acute effects on CBF compared with Ginkgo biloba and donepezil. CBF was measured by laser Doppler from rat cerebral cortex after 8 weeks of daily oral dosing of these drugs. Systolic blood pressure was also measured using the tail cuff method or via arterial cannulation. In rats treated with B. monnieri (40 mg/kg), CBF was 25% increased [2927 ± 123 perfusion units, (PU)] compared with shams (2337 ± 217 PU, p < 0.05, nine rats). G. biloba (60 mg/kg) also increased CBF (by 29% to 3019 ± 208 PU, p < 0.05, nine rats). No clear effect was obtained with donepezil (1 mg/kg). Chronic administration of the preparations had no effect on blood pressure. In contrast, intravenous acute infusion of these herbals (20-60 mg/kg) had marked dose-dependent hypotensive actions (diastolic ~31 mmHg lower with 40 mg/kg of either extract), which correspondingly reduced CBF by ~15%. Likewise, CBF fell slightly with acute intravenous sodium nitroprusside and rose with noradrenaline. Donepezil (1 mg/kg) was slightly hypotensive without affecting CBF. Increased CBF with B. monnieri may account for its reported procognitive effect, and its further exploration as an alternative nootropic drug is worthwhile.

Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (Brahmi) provides traditional cognitive treatments possibly reflecting improved cerebral hemodynamics. Little is known about the cardiovascular actions of Brahmi. We sought to assess its effects on blood pressure and on isolated arteries, thus providing insights to clinical applications. MATERIALS AND METHODS: Intravenous Brahmi (20-60 mg/kg) was tested on arterial blood pressure and heart rate of anaesthetized rats. In vitro vasorelaxation was assessed in arteries, with and without blockers of nitric oxide synthase (L-NAME), cyclooxygenase (indomethacin), and mechanical de-endothelialisation. The effects of Brahmi on Ca(2+) influx and release from stores were investigated. RESULTS: Intravenous Brahmi extract (20-60 mg/kg) decreased systolic and diastolic pressures without affecting heart rate. Brahmi evoked relaxation in isolated arteries in order of potency: basilar (IC50=102 ± 16 µg/ml)>mesenteric (171 ± 31)>aortae (213 ± 68)>renal (IC50=375 ± 51)>tail artery (494 ± 93)>femoral arteries (>1,000 µg/ml). Two saponins, bacoside A3 and bacopaside II, had similar vasodilator actions (IC50=8.3 ± 1.7 and 19.5 ± 6.3 µM). In aortae, without endothelium or in L-NAME (10-4M), Brahmi was less potent (IC50=213 ± 68 to 2170 ± 664 and 1192 ± 167 µg/ml, respectively); indomethacin (10-5M) was ineffective. In tail artery, Brahmi inhibited K(+)-depolarization induced Ca(2+) influx and Ca(2+) release from the sarcoplasmic reticulum by phenylephrine (10-5M) or caffeine (20mM). CONCLUSIONS: Brahmi reduces blood pressure partly via releasing nitric oxide from the endothelium, with additional actions on vascular smooth muscle Ca(2+) homeostasis. Some Brahmi ingredients could be efficacious antihypertensives and the vasodilation could account for some medicinal actions.

No effect of acute ingestion of Thai ginseng (Kaempferia parviflora) on sprint and endurance exercise performance in humans.

Thai ginseng, Kaempferia parviflora, is widely believed among the Mong hill tribe to reduce perceived effort and improve physical work capacity. Kaempferia parviflora is consumed before their daily work. Therefore, we conducted an acute study on the effects of K. parviflora on repeated bouts of sprint exercise and on endurance exercise time to exhaustion. Two studies were conducted in college males using a randomized, double-blind, crossover design. Ninety minutes after consumption of K. parviflora or a starch placebo, participants in study 1 (n = 19) completed three consecutive maximum 30-s sprint cycling Wingate tests, separated by 3 min recovery, while participants in study 2 (n = 16) performed submaximal cycling exercise to exhaustion. Peak and mean power output decreased with successive Wingate tests, while percent fatigue and blood lactate concentration increased after the third Wingate test (P < 0.05). There were no detectable differences in any measures with or without K. parviflora. There was also no effect of K. parviflora on time to exhaustion, rating of perceived exertion or heart rate during submaximal exercise. Our results indicate that acute ingestion of K. parviflora failed to improve exercise performance during repeated sprint exercise or submaximal exercise to exhaustion. However, chronic effects or actions in other populations cannot be excluded.