Efficacy of moxibustion in diarrhea-predominant irritable bowel syndrome model rats: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy of moxibustion in diarrhea-predominant irritable bowel syndrome (IBS-D) model rats. Methods: A comprehensive search was conducted in the China National Knowledge Infrastructure, WanFang Data, VIP, PubMed, Embase, and Web of Science databases from their inception to June 30, 2023. Relevant animal experiments investigating moxibustion for treating IBS-D in model rats were included. Two independent researchers screened the literature, extracted data, and evaluated the risk of bias in the selected studies. The meta-analysis was performed using RevMan 5.3 software. Results: In total, 21 animal studies comprising 680 model rats were included. The meta-analysis results demonstrated that moxibustion enhanced the threshold capacity of the abdominal withdrawal reflex (AWR) [standardized mean difference (SMD) = 1.84; 95% confidence interval (CI): 1.09, 2.60; p < 0.00001], ameliorated the rate of loose stool (SMD = -4.03; 95% CI: -5.76, -2.30; p < 0.00001), and decreased the colon 5-hydroxytryptamine (SMD = -3.67; 95% CI: -5.33, -2.01; p < 0.00001), serum interleukin-1ß (SMD = -3.24, 95% CI: -4.06, -2.41; p < 0.00001), serum tumor necrosis factor-α (SMD = -2.35, 95% CI: -4.12, -0.58; p < 0.00001), and serum substance P (SMD = -5.14, 95% CI: -8.45, -1.83; p = 0.002) concentrations. Moxibustion did not affect the blood calcitonin gene-related peptide level compared to the blank model group (p = 0.15). Conclusion: Moxibustion modulated the brain-gut interaction, reduced visceral hypersensitivity, inhibited intestinal inflammation, and regulated the immune balance, improving the rate of loose stool and increasing the AWR threshold capacity in IBS-D model rats, achieving good analgesic and antidiarrheal effects. However, these conclusions require further validation due to limitations in the quantity and quality of the included studies.

Altered Gut Microbiota is Involved in the Anti-Hypertensive Effects of Vitamin C in Spontaneously Hypertensive Rat.

SCOPE: Gut dysbiosis and dysregulation of the gut-brain-axis contributes to the pathogenesis of hypertension. Vitamin C (VC) is a common dietary supplement that shows the ability to lower the elevated blood pressure in hypertensive animals. Thus, the hypothesis that the gut microbiota is involved in the anti-hypertensive effect of VC is proposed. METHODS AND RESULTS: The changes of the gut microbiota and pathology in a spontaneously hypertensive rat (SHR) model after daily oral intake of VC in dosage of 200 or 1000 mg kg-1 are examined. After 4 weeks, the elevated blood pressure of SHRs in both VC-treated groups is attenuated. Sequencing of the gut microbiota shows improvement in its diversity and abundance. Bioinformatic analysis suggests restored metabolism and biosynthesis-related functions of the gut, which are confirmed by the improvement of gut pathology and integrity. Analysis of the hypothalamus paraventricular nucleus (PVN), the central pivot of blood pressure regulation, also shows reduced inflammatory responses and oxidative stress. CONCLUSIONS: The reduced blood pressure, enriched gut microbiota, improved gut pathology and integrity, and reduced inflammatory responses and oxidative stress in the PVN together suggest that the anti-hypertensive effects of VC involve reshaping of gut microbiota composition and function.

Exercise and food supplement of vitamin C ameliorate hypertension through improvement of gut microflora in the spontaneously hypertensive rats.

AIMS: Exercise and food supplement of vitamin C (VC) are beneficial to human health, especially for those who suffer from hypertension. Here we tend to explore if gut microflora is involved in the anti-hypertensive effects of exercise and VC-supplement therapies. MATERIALS AND METHODS: With the spontaneously hypertensive rat (SHR) model, the small intestine pathology and the fecal microbiota was analyzed along with the pro- and anti-inflammatory cytokines (PICs and AICs) and reactive oxygen species (ROS) in the hypothalamus paraventricular nucleus (PVN) and intestine. KEY FINDINGS: We found that both exercise and VC intake, individually or combined, were able to alleviate the blood pressure in the SHRs comparing to the normotensive control Wistar-kyoto (WKY) rats. The expression level of PICs in the PVN and intestine of the SHRs was down-regulated while the AICs were up-regulated after treatments, together with down-regulation of ROS in the PVN. At meantime, the gut pathology was dramatically improved in the SHRs with exercise training or VC intake. Analysis of the gut microflora revealed significant changes in their composition. Several important micro-organisms that were deficient in the SHRs were found up-regulated by the treatments, including Turicibacter and Romboutsia which are involved in the short-chain fatty acid production. SIGNIFICANCE: Exercise training and VC intake individually can modify the gut microflora composition and improve the inflammatory state in both PVN and intestine, which contribute to their anti-hypertensive function. Combination of the two treatments enhanced their effects and worth to be considered as a non-medical aid for the hypertensive patients.

Chronic infusion of berberine into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway.

BACKGROUND: Berberine (BBR), a Chinese traditional herbal medicine, has many pharmacologic benefits such as anti-inflammation and anti-oxidation. It is widely used in clinical treatment of cardiovascular diseases such as hypertension. However, the mechanism of how BBR attenuates hypertension through affecting central neural system is not clear. PURPOSE: This study was designed to determine whether chronic infusion of BBR into the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway. METHODS: Two-kidney, one-clip (2K1C) renovascular hypertensive rats were randomly assigned and treated with bilateral PVN infusion of BBR (2µg/h) or vehicle (artificial cerebrospinal fluid) via osmotic minipumps for 28 days. RESULTS: 2K1C rats showed higher mean arterial pressure (MAP) and PVN Fra-like activity, plasma levels of norepinephrine (NE), PVN levels of NOX2, NOX4, Erk1/2 and iNOS, and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD). Chronic infusion of BBR reduced MAP, PVN Fra-like activity and plasma levels of NE, reduced NOX2, NOX4, Erk1/2, iNOS and induced Cu/Zn-SOD in the PVN. CONCLUSIONS: These results suggest that BBR attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway in 2K1C renovascular hypertensive rats.

Tongxinluo improves cognition by decreasing ß-amyloid in spontaneous hypertensive rats.

ß-Amyloid (Aß) accumulation in the brain is the major pathophysiology of Alzheimer disease (AD). Hypertension is a risk factor for AD by promoting Aß deposition. Traditional Chinese medicinal compound tongxinluo (TXL) can improve blood circulation and endothelium-dependent vasodilation. This study investigates the effects of TXL on cognition and Aß using spontaneously hypertensive rats (SHRs). TXL was intragastrically administered to SHRs at low-dose, mid-dose and high-dose for 15, 30 or 60days. Cognition was evaluated with a Morris Water Maze (MWM). Aß in the brain was detected by western blot, ELISA and Thioflavin-S staining. Western blot and RT-PCR were employed to exam the expression of receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein-1 (LRP-1) and amyloid precursor protein (APP). After TXL treatment for 60days, compared with the vehicle, the number of crossed platform and the time spent in the target quadrant increased in parallel with the increasing length of treatment in MWM. Moreover, the Aß in the hippocampus significantly decreased compared to the vehicle group, both in western blot and ELISA. Additionally, TXL reduced RAGE expression in a dose- and time-depended manner, but LRP-1 expression had no difference between TXL groups and vehicle groups. Furthermore, the ß-secretase expression was significantly decreased compared to the vehicle group, but APP expression had no difference. In conclusion, TXL improved cognition and decreased Aß in SHRs in a dose- and time-dependent manner, the underlying mechanism may involved in inhibiting RAGE and ß-secretase expression.

Alpha lipoic acid supplementation attenuates reactive oxygen species in hypothalamic paraventricular nucleus and sympathoexcitation in high salt-induced hypertension.

AIMS: High salt-induced oxidative stress plays an important role in the development of hypertension. Alpha lipoic acid (ALA) is extensively recognized as having a powerful superoxide inhibitory property. In this study, we determined whether ALA supplementation attenuates oxidative stress in hypothalamic paraventricular nucleus (PVN), decreases the sympathetic activity and arterial pressure in high salt-induced hypertension by cross-talking with renin-angiotensin system (RAS) and pro-inflammatory cytokines (PICs). METHODS: Male Wistar rats were administered a normal-salt diet (NS, 0.3% NaCl) or a high-salt diet (HS, 8.0% NaCl) for 8 weeks. These rats received ALA (60mg/kg) dissolved in vehicle (0.9% saline) or an equal voleme of vehicle, by gastric perfusion for 9 weeks. RESULTS: High salt intake resulted in higher renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). These rats also had higher levels of superoxide, gp91(phox), gp47(phox) (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), angiotensin II type1 receptor (AT1-R), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and lower levels of interleukin-10 (IL-10) and copper/zinc superoxide dismutase (Cu/Zn-SOD) than control animals. Treatment with ALA significantly attenuated the levels of superoxide, gp91(phox), gp47(phox), ACE, AT1-R, IL-1ß and IL-6, increased the levels of IL-10 and Cu/Zn-SOD, and decreased MAP and RSNA compared with high-salt induced hypertensive rats. The mRNA expression of gp47(phox) and gp91(phox) are in accordance with their protein expression. CONCLUSION: These findings suggest that supplementation of ALA obviously decreases the sympathetic activity and arterial pressure in high salt-induced hypertension by improving the superoxide inhibitory property, suppressing the activation of RAS and restoring the balance between pro- and anti-inflammatory cytokines in the PVN.

Central blockade of salusin ß attenuates hypertension and hypothalamic inflammation in spontaneously hypertensive rats.

Salusin ß is a multifunctional bioactive peptide and is considered as a promising candidate biomarker for predicting atherosclerotic cardiovascular diseases. The present study was designed to investigate the roles and mechanisms of salusin ß in the paraventricular nucleus (PVN) in attenuating hypertension and hypothalamic inflammation and whether central salusin ß blockade has protective effects in essential hypertension. Normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were used in this study. The rats were chronic PVN infusion either specific salusin ß blocker, antisalusin ß IgG (SIgG), or control IgG (CIgG) for 2 weeks. Hypertensive rats had significantly increased salusin ß expression compared with normotensive rats. Central blockade of salusin ß attenuated hypertension, reduced circulating norepinephrine (NE) levels, and improved cardiac hypertrophy and function in hypertensive rats. Salusin ß blockade significantly reduced proinflammatory cytokines (PICs), nuclear factor-kappa B (NF-κB) activity, reactive oxygen species (ROS) levels, and altered renin-angiotensin system (RAS) components in the PVN of hypertensive rats. These findings suggest that the beneficial effects of salusin ß blockade in essential hypertension are possibly due to down-regulate of inflammatory molecules and ROS in the PVN.