Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored. However, it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system., and has accordingly been a focus of extensive clinical research. As a traditional Chinese medicinal formulation, Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases. Its main constituents include Citrus aurantium, Magnolia officinalis, rhubarb, and Qiangwu, which are primarily used to regulate qi. In the treatment of neurological diseases, the therapeutic effects of the Sanhua Decoction are mediated via different pathways, including antioxidant, anti-inflammatory, and neurotransmitter regulatory pathways, as well as through the protection of nerve cells and a reduction in cerebral edema. Among the studies conducted to date, many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects. In addition, as a natural treatment, the Sanhua Decoction has received widespread attention, given that it is safer and more effective than traditional Western medicines. Consequently, research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance. In this paper, we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction. We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion, and provide a scientific basis for its application in clinical practice.

Aloe-emodin from Sanhua Decoction inhibits neuroinflammation by regulating microglia polarization after subarachnoid hemorrhage.

ETHNOPHARMACOLOGICAL RELEVANCE: Subarachnoid hemorrhage (SAH) triggers a cascade of events that lead to early brain injury (EBI), which contributes to poor outcomes and appears within 3 days after SAH initiation. EBI involves multiple process including neuronal death, blood-brain barrier (BBB) injury and inflammation response. Microglia are cluster of immune cells originating in the brain which respond to SAH by changing their states and releasing inflammatory molecules through various signaling pathways. M0, M1, M2 are three states of microglia represent resting state, promoting inflammation state, and anti-inflammation state respectively, which can be modulated by pharmacological strategies. AIM OF THE STUDY: After identified potential active ingredients and targets of Sanhua Decoction (SHD) for SAH, we selected aloe-emodin (AE) as a potential ingredient modulating microglia activation states. MATERIALS AND METHODS: Molecular mechanisms, targets and pathways of SHD were reveal by network pharmacology technique. The effects of AE on SAH were evaluated in vivo by assessing neurological deficits, neuronal apoptosis and BBB integrity in a mouse SAH model. Furthermore, BV-2 cells were used to examine the effects of AE on microglial polarization. The influence of AE on microglia transformation was measured by Iba-1, TNF-α, CD68, Arg-1 and CD206 staining. The signal pathways of neuronal apoptosis and microglia polarization was measured by Western blot. RESULTS: Network pharmacology identified potential active ingredients and targets of SHD for SAH. And AE is one of the active ingredients. We also confirmed that AE via NF-κB and PKA/CREB pathway inhibited the microglia activation and promoted transformation from M1 phenotype to M2 at EBI stage after SAH. CONCLUSIONS: AE, as one ingredient of SHD, can alleviate the inflammatory response and protecting neurons from SAH-induced injury. AE has potential value for treating SAH-induced nerve injury and is expected to be applied in clinical practice.

Sanhua decoction: Current understanding of a traditional herbal recipe for stroke.

Both thrombolytic and endovascular therapies are optimal treatment options for patients with acute ischemic stroke, but only less than half of these patients can benefit from these treatments. Traditional Chinese medicine has a long history of successfully managing ischemic stroke using both herbal and physical therapeutics. Among herbal recipes, Sanhua decoction (SHD) is one of the classical prescriptions for ischemic stroke. The present review aimed to summarize evidence from both clinical and basic research to demonstrate its efficacy in managing ischemic stroke and the potential mechanisms underlying its therapeutic effects, which will provide evidence on the therapeutic effect of this herbal recipe and guide future studies on this recipe. SHD is composed of four herbs, Rheum palmatum L. [Polygonaceae], Magnolia officinalis Rehder & E.H.Wilson [Magnoliaceae], Citrus × aurantium L. [Rutaceae], Hansenia weberbaueriana (Fedde ex H.Wolff) Pimenov & Kljuykov [Apiaceae]. We found that the majority of clinical studies on SHD are case reports and they showed positive therapeutic effect of SHD on both acute and chronic ischemic stroke. There are over 40 bioactive compounds identified in SHD, but few experimental studies have examined their individual molecular mechanisms. As an extract of SHD, it improves neurological functions through suppressing inflammation, protecting the blood brain barrier from degradation, restoring the number of neural stem cells, inhibiting apoptosis and brain edema, scavenging oxygen free radicals, and regulating the brain-gut axis. These will lay the theoretical foundation for future studies on this prescription and its clinical application. Future research may need to confirm its clinical efficacy in large-scale clinical trials and to disentangle its bioactive compounds and their potential mechanisms.

[Clinical observational study on the treatment of oligozoospermia with Shizi Sanhua decoction combined with Nuoyu].

OBJECTIVE: To study the clinical therapeutic effect as well as drug effectiveness and safety of Shizi Sanhua decoction combined with Nuoyu in the treatment of oligozoospermia in men. METHODS: 102 patients with oligozoospermia diagnosed at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from February 2022 to March 2023 were selected and randomly divided into 3 groups. The treatment group was treated with Shizi Sanhua Decoction + Nuoyu; the traditional Chinese medicine group was treated with Shizi Sanhua Decoction; and the Nuoyu nutrient group was treated with Nuoyu nutrient. A review assessment and record were made after one course of treatment (3 months). RESULTS: A total of 102 patients completed the trial due to the treatment process. There were 34 cases in each of the traditional Chinese medicine group, the Nuoyu nutrient group, and the treatment group. Clinical efficacy: total effective rate of 52.94% in the traditional Chinese medicine group; 58.82% in the Nuoyu nutrient group; 82.35% in the treatment group. The clinical efficacy of the treatment group was better than that of the traditional Chinese medicine group and the Nuoyu nutrient group (P<0.05), which was statistically significant. Semen routine: the treatment group was better than the traditional Chinese medicine group and Nuoyu nutrient group in improving the total number of sperm and sperm concentration. CONCLUSION: The semen concentration and forward sperm count of patients with oligozoospermia treated with Shizi Sanhua Decoction combined with Nuoyu improved more significantly, and the clinical efficacy was remarkable. And the clinical efficacy is not affected by age and disease duration. It can be popularized and applied as a treatment for oligozoospermia.

Determination of active ingredients and prediction of targetin Sanhua Decoction for cerebral ischemia based on HPLC and network pharmacology methods / 国际中医中药杂志

Objective:To determinate the active ingredients and predicte action targets in Sanhua Decoction for treating cerebral ischemia based on HPLC and network pharmacology methods. Methods:The HPLC analysis was performed on HC-C18 (250 mm × 4.6 mm, 5 μm) with the mobile phase of methanolacetonitrile-0.05% phosphoric acid with gradient elution at the flow rate of 1.0 ml/min and 0.8 ml/min. The detection wavelength was set at 254 nm, the column temperature was at 30 ℃, and the injection volume was 10 μl. TCMIP v2.0 platform was used to search the action targets of rhein, emodin, chrysophanol, hesperidin, magnolol and notopterygiol. We used Cerebral ischemia as a keyword searching the databases such as Genecards, OMIM, TTD, and Disgenet to screen six potential targets for the treatment of cerebral ischemia by active ingredients, construct a protein interaction (PPI) network and a disease-component-target-pathway integration network.Results:The literature search determined that rhein, emodin, chrysophanol, hesperidin, magnolol and qianhuol were the index components for the determination of Sanhua Decoction. Their linear ranges were 0.080 4-0.804 0 μg, 0.015 3-0.382 0 μg, 0.041 8-0.626 4 μg, 0.312 6-3.908 0 μg, 0.037 9-0.568 8 μg, 0.045 3-1.359 6 μg, respectively. The correlation coefficient R 2 is greater than 0.999 0. The content ranges of the above six components in seven samples were 0.887-0.971 mg/g, 0.094-0.101 mg/g, 0.110-0.119 mg/g, 1.494-1.669 mg/g, 0.126-0.145 mg/g and 0.153-0.167 mg/g, respectively. Network pharmacology analysis found that the targets of the six components for the treatment of cerebral ischemia may be TNF, TP53, MAPK14, JUN, IL1B, MYC, ESR1, ICAM1, PTGS2, PPARG and so on. Conclusions:A quality control method forthe six active ingredients in Sanhua Decoction treating cerebral ischemia was established. This method is simple and repeatable. The ten potential targets of the six active ingredients in Sanhua Decoction for the treatment of cerebral ischemia have been clarified, laying a foundation for further research on the action mechanism.