Antihypertensive effect and mechanism of the traditional recipe of medicine food homology (Buyang Huanwu Decoction) in China: Meta analysis and network pharmacological exploration.

Background: Hypertension has become a part of the lives of many people worldwide. With the development, an increasing number of people have begun to control their hypertension through products of medicine food homology, such as Buyang Huanwu Decoction (BYHWD). However, there has been no objective review of the regulation of hypertension by BYHWD. Methods: As of 9 October 2023, this review made a detailed search of nine databases to look for random controlled trials (RCTs) focused on the use of BYHWD for treating hypertension. This was followed by network pharmacological analysis, and molecular docking assessment using AutoDockTools to explore the mode of action. Results: BYHWD was effective in reducing SBP (MD: 0.767; 95 % CI: 0.629, 0.905; p = 0.000), DBP (MD: 0.427; 95 % CI: 0.292, 0.561; p = 0.000), 24h SBP (MD: 0.665; 95 % CI: 0.368, 0.962; p = 0.000), 24h DBP (MD: 0.547; 95 % CI: 0.318, 0.777; p = 0.000), dSBP (MD: 0.625; 95 % CI: 0.395, 0.855; p = 0.000), dDBP (MD: 0.632; 95 % CI: 0.401, 0.862; p = 0.000), nSBP (MD: 0.859; 95 % CI: 0.340, 1.377; p = 0.001), nDBP (MD: 0.704; 95 % CI: 0.297, 1.112; p = 0.001), pv (MD: 1.311; 95 % CI: 0.363, 2.259; p = 0.007) and NIHSS (MD: 1.149; 95 % CI: 0.100, 2.199; p = 0.032), and elevating CER (OR = 2.848; 95 % CI: 1.388, 5.843; p = 0.004). However, BYHWD did not significantly reduce HCY, and there was no significant difference in the incidence of AE. In terms of the mechanism of action, the main active ingredient of BYHWD is quercetin, and the core targets are AKT1, MMP9, and others. Molecular docking also showed that quercetin mainly interacts with the amino acid residue CYS-28 of MMP2. Second, the KEGG analysis showed that BYHWD mainly act on HIF-1, Apelin, and cGMP-PKG signalling pathways, and GO analysis showed that it related to the apical part of the cell, circulatory system processes, and nuclear receptor activity. Conclusion: BYHWD can lowered blood pressure, reduced plasma viscosity, and restored neurological function with good tolerability, and had no significant effect on HCY levels. This study further demonstrated that quercetin is the main active ingredient of BYHWD that acts via the AKT1 and HIF-1 signalling pathways. These results provide new guidance for people's dietary choices by the general public.

The SALT OVERLY SENSITIVE 2-CONSTITUTIVE TRIPLE RESPONSE1 module coordinates plant growth and salt tolerance in Arabidopsis.

High salinity stress promotes plant ethylene biosynthesis and triggers the ethylene signalling response. However, the precise mechanism underlying how plants transduce ethylene signalling in response to salt stress remains largely unknown. In this study, we discovered that SALT OVERLY SENSITIVE 2 (SOS2) inhibits the kinase activity of CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) by phosphorylating the 87th serine (S87). This phosphorylation event activates the ethylene signalling response, leading to enhanced plant salt resistance. Furthermore, through genetic analysis, we determined that the loss of CTR1 or the gain of SOS2-mediated CTR1 phosphorylation both contribute to improved plant salt tolerance. Additionally, in the sos2 mutant, we observed compromised proteolytic processing of ETHYLENE INSENSITIVE 2 (EIN2) and reduced nuclear localization of EIN2 C-terminal fragments (EIN2-C), which correlate with decreased accumulation of ETHYLENE INSENSITIVE 3 (EIN3). Collectively, our findings unveil the role of the SOS2-CTR1 regulatory module in promoting the activation of the ethylene signalling pathway and enhancing plant salt tolerance.

How Plants Tolerate Salt Stress.

Soil salinization inhibits plant growth and seriously restricts food security and agricultural development. Excessive salt can cause ionic stress, osmotic stress, and ultimately oxidative stress in plants. Plants exclude excess salt from their cells to help maintain ionic homeostasis and stimulate phytohormone signaling pathways, thereby balancing growth and stress tolerance to enhance their survival. Continuous innovations in scientific research techniques have allowed great strides in understanding how plants actively resist salt stress. Here, we briefly summarize recent achievements in elucidating ionic homeostasis, osmotic stress regulation, oxidative stress regulation, and plant hormonal responses under salt stress. Such achievements lay the foundation for a comprehensive understanding of plant salt-tolerance mechanisms.

Phytochromes enhance SOS2-mediated PIF1 and PIF3 phosphorylation and degradation to promote Arabidopsis salt tolerance.

Soil salinity is one of the most detrimental abiotic stresses affecting plant survival, and light is a core environmental signal regulating plant growth and responses to abiotic stress. However, how light modulates the plant's response to salt stress remains largely obscure. Here, we show that Arabidopsis (Arabidopsis thaliana) seedlings are more tolerant to salt stress in the light than in the dark, and that the photoreceptors phytochrome A (phyA) and phyB are involved in this tolerance mechanism. We further show that phyA and phyB physically interact with the salt tolerance regulator SALT OVERLY SENSITIVE2 (SOS2) in the cytosol and nucleus, and enhance salt-activated SOS2 kinase activity in the light. Moreover, SOS2 directly interacts with and phosphorylates PHYTOCHROME-INTERACTING FACTORS PIF1 and PIF3 in the nucleus. Accordingly, PIFs act as negative regulators of plant salt tolerance, and SOS2 phosphorylation of PIF1 and PIF3 decreases their stability and relieves their repressive effect on plant salt tolerance in both light and dark conditions. Together, our study demonstrates that photoactivated phyA and phyB promote plant salt tolerance by increasing SOS2-mediated phosphorylation and degradation of PIF1 and PIF3, thus broadening our understanding of how plants adapt to salt stress according to their dynamic light environment.

SALT OVERLY SENSITIVE 1 is inhibited by clade D Protein phosphatase 2C D6 and D7 in Arabidopsis thaliana.

The salt overly sensitive (SOS) pathway is essential for maintaining sodium ion homeostasis in plants. This conserved pathway is activated by a calcium signaling-dependent phosphorylation cascade. However, the identity of the phosphatases and their regulatory mechanisms that would deactivate the SOS pathway remain unclear. In this study, we demonstrate that PP2C.D6 and PP2C.D7, which belong to clade D of the protein phosphatase 2C (PP2C) subfamily in Arabidopsis thaliana, directly interact with SOS1 and inhibit its Na+/H+ antiporter activity under non-salt-stress conditions. Upon salt stress, SOS3-LIKE CALCIUM-BINDING PROTEIN8 (SCaBP8), a member of the SOS pathway, interacts with the PP2Cs and suppresses their phosphatase activity; simultaneously, SCaBP8 regulates the subcellular localization of PP2C.D6 by releasing it from the plasma membrane. Thus, we identified two negative regulators of the SOS pathway that repress SOS1 activity under nonstress conditions. These processes set the stage for the activation of SOS1 by the kinase SOS2 to achieve plant salt tolerance. Our results suggest that reversible phosphorylation/dephosphorylation is crucial for the regulation of the SOS pathway, and that calcium sensors play dual roles in activating/deactivating SOS2 and PP2C phosphatases under salt stress.

Screening of protonstatin-1 (PS-1) analogs for improved inhibitors of plant plasma membrane H+-ATPase activity.

We previously identified protonstatin-1 (PS-1) as a selective inhibitor of plasma membrane H+-ATPase (PM H+-ATPase) activity and used it as a tool to validate the chemiosmotic model for polar auxin transport. Here, to obtain compounds with higher affinity than PS-1 for PM H+-ATPase, we synthesized 34 PS-1 analogs and examined their ability to inhibit PM H+-ATPase activity. The 34 analogs showed varying inhibitory effects on the activity of this enzyme. The strongest effect was observed for the small molecule PS-2, which was approximately five times stronger than PS-1. Compared to PS-1, PS-2 was also a stronger inhibitor of auxin uptake as well as acropetal and basipetal polar auxin transport in Arabidopsis thaliana seedlings. Because PS-2 is a more potent inhibitor of PM H+-ATPase than PS-1, we believe that this compound could be used as a tool to study the functions of this key plant enzyme.

Phosphatidic acid inhibits SCAB1-mediated F-actin bundling in Arabidopsis.

Stomatal closure-associated actin-binding protein 1 (SCAB1) regulates stomatal closure by mediating actin filament reorganization in Arabidopsis thaliana. Our previous study showed that phosphatidylinositol 3-phosphate (PI3P) binds to SCAB1 and inhibits its oligomerization, thereby inhibiting its activity on F-actin in guard cells during stomatal closure. In this study, we show that another phospholipid, phosphatidic acid (PA), also binds to SCAB1 and inhibits its actin-bundling activity but not its actin-binding activity. F-actin bundling was promoted in vivo by treating Col-0 seedlings with n-butanol, a suppressor of PA production, but this effect was absent in the scab1 mutant. These results indicate that the signaling molecule PA is involved in the modulation of SCAB1 activity in F-actin reorganization.

SCaBP3/CBL7 negatively regulates the plasma membrane H+-ATPase and modulates hypocotyl elongation in Arabidopsis.

The regulation of hypocotyl elongation is an important process in plant growth and development and depends on the activity of the plasma membrane (PM) H+-ATPase. In this study, we found that the Arabidopsis protein SOS3-LIKE CALCIUM BINDING PROTEIN3 (SCaBP3) negatively regulates PM H+-ATPase activity in yeast and hypocotyl elongation in dark-grown seedlings. Yeast two-hybrid assays showed that SCaBP3 interacts with representative members of the Arabidopsis PM H+-ATPase family. Experiments in RS-72 yeast showed that SCaBP3 negatively regulates PM H+-ATPase activity-dependent yeast cell growth. Hypocotyl elongation was promoted in the loss-of-function mutant scabp3 and inhibited in SCaBP3 overexpression lines of Arabidopsis. We propose that SCaBP3 modulates hypocotyl elongation by negatively regulating PM H+-ATPase activity.

Efficacy and safety of micronized purified flavonoid fractions for the treatment of postoperative hemorrhoid complications: A systematic review and meta-analysis.

BACKGROUND: Hemorrhoids, a common anorectal disease, seriously affects patients' quality of life. Micronized purified flavonoid fractions (MPFF) have been shown to improve hemorrhoid symptoms. PURPOSE: To evaluate the efficacy and safety of MPFF in treating postoperative hemorrhoid complications. STUDY DESIGN: A systematic review and meta-analysis of existing literature on natural compounds for treating postoperative complications of hemorrhoids. METHODS: A literature search was conducted using five databases, namely PubMed, WanFang, CNKI, Embase, and the Cochrane Library, to identify randomized controlled trials (RCTs) on the effects of MPFF treatment on hemorrhoids. Stata 15.1 and Revman 15.4 were used to assess the data, while subgroup and sensitivity analyses were performed to evaluate potential heterogeneity, and trial sequential analysis (TSA) and Egger test were used to evaluate the reliability of each trial. RESULTS: A total of 22 RCTs, including 2,335 participants were included in the analysis. MPFF improved the clinical efficacy of post-hemorrhoidectomy and reduced the bleeding rate, pain score, and edema score, although no substantial effect on adverse reactions was reported. Subgroup analyses showed a significant reduction in pain score and bleeding rate in trials with duration of 4-10 days and an improvement in clinical efficacy. Treatment for ≥ 10 days significantly improved the edema score; a dosage range of 1,800-2,700 mg/day of MPFF significantly reduced edema and pain scores, whereas < 1,800 mg/day significantly improved clinical efficacy. CONCLUSIONS: Based on searching the relevant literatures, this is the first meta-analysis on MPFF treatment of postoperative hemorrhoid complications. Our findings, validated by TSA, suggest that MPFF is safe and effective in reducing postoperative hemorrhoid complications, and that dose and duration are key factors in its efficacy, as illustrated by subgroup analysis. However, due to the small sample size, the standardized treatment regimen of MPFF could not be obtained; therefore, further research is warranted.

Dynamic changes of phosphatidylinositol and phosphatidylinositol 4-phosphate levels modulate H+-ATPase and Na+/H+ antiporter activities to maintain ion homeostasis in Arabidopsis under salt stress.

Plant metabolites are dynamically modified and distributed in response to environmental changes. However, it is poorly understood how metabolic change functions in plant stress responses. Maintaining ion homeostasis under salt stress requires coordinated activation of two types of central regulators: plasma membrane (PM) H+-ATPase and Na+/H+ antiporter. In this study, we used a bioassay-guided isolation approach to identify endogenous small molecules that affect PM H+-ATPase and Na+/H+ antiporter activities and identified phosphatidylinositol (PI), which inhibits PM H+-ATPase activity under non-stress conditions in Arabidopsis by directly binding to the C terminus of the PM H+-ATPase AHA2. Under salt stress, the phosphatidylinositol 4-phosphate-to-phosphatidylinositol (PI4P-to-PI) ratio increased, and PI4P bound and activated the PM Na+/H+ antiporter. PI prefers binding to the inactive form of PM H+-ATPase, while PI4P tends to bind to the active form of the Na+/H+ antiporter. Consistent with this, pis1 mutants, with reduced levels of PI, displayed increased PM H+-ATPase activity and salt stress tolerance, while the pi4kß1 mutant, with reduced levels of PI4P, displayed reduced PM Na+/H+ antiporter activity and salt stress tolerance. Collectively, our results reveal that the dynamic change between PI and PI4P in response to salt stress in Arabidopsis is crucial for maintaining ion homeostasis to protect plants from unfavorable environmental conditions.

The SOS2-SCaBP8 Complex Generates and Fine-Tunes an AtANN4-Dependent Calcium Signature under Salt Stress.

Calcium signals act as universal second messengers that trigger many cellular processes in animals and plants, but how specific calcium signals are generated is not well understood. In this study, we determined that AtANN4, a putative calcium-permeable transporter, and its interacting proteins, SCaBP8 and SOS2, generate a calcium signal under salt stress, which initially activates the SOS pathway, a conserved mechanism that modulates ion homeostasis in plants under salt stress. After activation, SCaBP8 promotes the interaction of protein kinase SOS2 with AtANN4, which enhances its phosphorylation by SOS2. This phosphorylation of AtANN4 further increases its interaction with SCaBP8. Both the interaction with and phosphorylation of AtANN4 repress its activity and alter calcium transients and signatures in HEK cells and plants. Our results reveal how downstream targets are required to create a specific calcium signal via a negative feedback regulatory loop, thereby enhancing our understanding of the regulation of calcium signaling.

Diuretic of choice in ABFM hypertension self-assessment module simulations.

BACKGROUND: Evidence suggests that chlorthalidone has therapeutic advantages over hydrochlorothiazide, perhaps because of a longer antihypertensive effect. Although guidelines such as the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure treat diuretics as a class, some experts believe chlorthalidone is the diuretic of choice in hypertension management. We evaluated diplomates' use of chlorthalidone and hydrochlorothiazide as first-choice diuretics in virtual patient simulations of hypertension in the American Board of Family Medicine Maintenance of Certification for Family Physicians self-assessment modules. METHODS: We examined action logs for hypertension simulations completed between 2004 and 2011 and identified initial antihypertensive choices made by diplomates. We tabulated uses of any diuretic as initial treatment, distinguishing between chlorthalidone, hydrochlorothiazide, and other diuretic choices. We examined trends in the use of diuretics and chlorthalidone in simulations using linear models. RESULTS: Chlorthalidone use increased 0.7 percentage points per year (test for ß >0, P < .0013), from approximately 1.3% of simulation prescriptions in 2004 to about 4.8% in 2010 and 2011, whereas hydrochlorothiazide prescriptions fell 2 percentage points per year (P = .035), from nearly 57% to 47%. As a fraction of all diuretic use, chlorthalidone increased 1.4 percentage points per year (P = .0006), from 2% to 9%. CONCLUSIONS: Small but growing numbers of diplomates are heeding recommendations in the growing literature to start with chlorthalidone rather than hydrochlorothiazide, at least in the virtual patient environment. Observed choices in virtual patient management strongly imply that this is a valid topic for additional attention in the hypertension self-assessment module.

Family physicians' completion of scoring criteria in Virtual Patient encounters.

The American Board of Family Medicine (ABFM) has used a 60-item Multiple Choice Question (MCQ) section followed by a Virtual Patient (VP) exercise in Maintenance Of Certification (MOC) since 2004, and has had an asthma module since 2005. The original asthma VP criteria anticipated some Expert Panel Report-3 recommendations, such as home peak flow monitoring and a written plan, that were added to the MCQ section only when the guideline was updated in 2007. VP completion rates for these criteria improved markedly with the MCQ update, while other criteria completion rates were stable. Asthma criteria completion rates are not predicted by the strength of evidence for the criteria. User interface details influence criteria completion rates, but did not affect the changes observed in 2007. Asthma MCQ content affects Diplomate performance on asthma VP: this translational step suggests that MOC exercises could result in improved care for real patients.