Effect and mechanism of Jinkui Shenqi Pill on preventing neural tube defects in mice based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: jinkui Shenqi Pill (JSP) is a classic traditional Chinese medicine used to treat "Kidney Yang Deficiency" disease. Previous studies indicate a protective effect of JSP on apoptosis in mouse neurons. AIM OF THE STUDY: This research, combining network pharmacology with in vivo experiments, explores the mechanism of JSP in preventing neural tube defects (NTDs) in mice. MATERIALS AND METHODS: Network pharmacology analyzed JSP components and targets, identifying common genes with NTDs and exploring potential pathways. Molecular docking assessed interactions between key JSP components and pathway proteins. In an all-trans retinoic acid (atRA)-induced NTDs mouse model, histopathological changes were observed using HE staining, neuronal apoptosis was detected using TUNEL, and Western Blot assessed changes in the PI3K/AKT signaling pathway and apoptosis-related proteins. RESULTS: Different concentrations of JSP led to varying degrees of reduction in the occurrence of neural tube defects in mouse embryos, with the highest dose showing the most significant decrease. Furthermore, it showed a better reduction in NTDs rates compared to folic acid (FA). Network pharmacology constructed a Drug-Active Ingredient-Gene Target network, suggesting key active ingredients such as Quercetin, Wogonin, Beta-Sitosterol, Kaempferol, and Stigmasterol, possibly acting on the PI3K/Akt signaling pathway. Molecular docking confirmed stable binding structures. Western Blot analysis demonstrated increased expression of p-PI3K, p-Akt, p-Akt1, p-Akt2, p-Akt3, downregulation of cleaved caspase-3 and Bax, and upregulation of Bcl-2, indicating prevention of NTDs through anti-apoptotic effects. CONCLUSION: We have identified an effective dosage of JSP for preventing NTDs, revealing its potential by activating the PI3K/Akt signaling pathway and inhibiting cell apoptosis in atRA-induced mouse embryonic NTDs.

Integrated serum pharmacochemistry, network pharmacology, and pharmacokinetics to clarify the effective components and pharmacological mechanisms of the proprietary Chinese medicine Jinkui Shenqi Pill in treating kidney yang deficiency syndrome.

The proprietary Chinese medicine Jinkui Shenqi Pill (PCM-JKSQP) is a classic compound used for the effective clinical treatment of kidney yang deficiency syndrome (KYDS), a metabolic disease accompanied by kidney injury. However, its active ingredients and therapeutic mechanisms are not clear. This study employed serum pharmacochemistry, network pharmacology, and pharmacokinetics (PK) to identify the bioactive components of PCM-JKSQP and preliminarily clarify its mechanism in treating KYDS. One hundred and forty chemical components of PCM-JKSQP, 47 (20 parent compouds and 27 metabolites) of which were absorbed into the blood, were identified by ultra-high-performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). The topological parameters of network pharmacology and high concentrations in blood found six parent components as PK markers (cinnamic acid, paeonol, loganin, morroniside, apigenin, and poricoic acid A). PK analysis further identified these six compounds as active ingredients. Protein-protein interaction (PPI) analysis and molecular docking simulation predicted and verified eight core targets (TP53, ESR1, CTNNB1, EP300, EGFR, AKT1, ERBB2, and TNF). Most were concentrated in the MAPK, HIF-1, and PI3K-AKT signaling pathways, indicating that these six active ingredients may mainly exert therapeutic effects through these three pathways via their core targets. The PK results also showed these six components were absorbed quickly, although cinnamic acid and paeonol were rapidly metabolized, with a short half-life and retention time. Loganin and morroniside did not have high peak concentrations, and apigenin and poricoic acid A had long retention times. This study provides a new overall perspective for exploring the bioactive components and mechanisms underlying the effects of PCM-JKSQP in treating KYDS.

Effects of Jinkui Shenqi and Wuzi Yanzong pill on sperm motility and sperm DNA fragmentation rate in asthenospermia

This study was designed to compare the effects of Jinkui Shenqi and Wuzi Yanzong pill on sperm motility and sperm DNA fragmentation rate in patients with asthenospermia. 130 cases were randomly divided into an observation and control group (n=65). The control group was treated with the Wuzi Yanzong pill while the observation group with the Jinkui Shenqi pill. The sperm motility parameters rate (PR), semen concentration, sperm motility, DFI and α-glucosidase, fructose, seminal plasma zinc (Zn), acid phosphatase (ACP) in seminal plasma biochemistry and other indexes of were observed. The biochemical indexes of seminal plasma of α-glucosidase, fructose, Zn, ACP in two groups were significantly (p<0.05) improved after treatment. Compared with the control group, the indexes of the observation group improved more obviously after treatment. Pearson correlation analysis of DFI and PR indexes in 130 patients before treatment showed that sperm DFI and PR percentage were negatively correlated in asthenospermia patients (r =-0.572, P<0.05). There was no significant difference in DFI, semen concentration, PR, and sperm motility between the two groups before treatment. The DFI, semen concentration, PR and sperm viability of the two groups showed a tendency to improve after treatment, and the effect of the observation group was less significant than that of the control group (p<0.05). Two groups of patients have completed treatment successfully, no adverse events occurred during treatment. Jinkui Shenqi pill can effectively treat asthenospermia, which can effectively improve the effect of sperm motility in patients. It has less adverse reactions, safe and reliable, and is worthy of promotion.

Global and Targeted Metabolomics Evidence of the Protective Effect of Chinese Patent Medicine Jinkui Shenqi Pill on Adrenal Insufficiency after Acute Glucocorticoid Withdrawal in Rats.

Glucocorticoids are commonly used in anti-inflammatory and immunomodulatory therapies, but glucocorticoid withdrawal can result in life-threatening risk of adrenal insufficiency. Chinese patented pharmaceutical product Jinkui Shenqi pill (JKSQ) has potent efficacy on clinical adrenal insufficiency resulting from glucocorticoid withdrawal. However, the underlying molecular mechanism remains unclear. We used an animal model to study JKSQ-induced metabolic changes under adrenal insufficiency and healthy conditions. Sprague-Dawley rats were treated with hydrocortisone for 7 days with or without 15 days of JKSQ pretreatment. Sera were collected after 72 h hydrocortisone withdrawal and used for global and free fatty acids (FFAs)-targeted metabolomics analyses using gas chromatography/time-of-flight mass spectrometry and ultraperformance liquid chromatography/quadruple time-of-flight mass spectrometry. Rats without hydrocortisone treatment were used as controls. JKSQ pretreatment normalized the significant changes of 13 serum metabolites in hydrocortisone-withdrawal rats, involving carbohydrates, lipids, and amino acids. The most prominent effect of JKSQ was on the changes of FFAs and some [product FFA]/[precursor FFA] ratios, which represent estimated desaturase and elongase activities. The opposite metabolic responses of JKSQ in adrenal insufficiency rats and normal rats highlighted the "Bian Zheng Lun Zhi" (treatment based on ZHENG differentiation) guideline of TCM and suggested that altered fatty acid metabolism was associated with adrenal insufficiency after glucocorticoid withdrawal and the protective effects of JKSQ.

Clinical Observation of Jinkui Shenqi Pill versus Shengjing Capsule in the Treatment of Oligoasthenozoosper-mia under Behavioral Intervention / 中国药房

OBJECTIVE:To compare the efficacy and safety of Jinkui shenqi pill versus Shengjing capsule in the treatment of oligoasthenozoosperimia under behavioral intervention. METHODS:98 patients with oligoasthenozoosperimia were randomly divid-ed into Shengjing capsule group(49 cases)and Jinkui shenqi pill(49 cases). All patients received intervention treatment(cognitive intervention,psychological intervention,diet intervention and exercise intervention,etc.). Based on it,Shengjing capsule group re-ceived 1.6 g Shengjing capsules,orally,3 times a day;Jinkui shenqi pill group received 6 g Jinkui shenqi pill,orally,twice a day. They were treated for 3 months. Clinical efficacy,semen quality (semen volume,sperm concentration,sperm motility rate, sperm motility)and sex hormone levels [testosterone(T),follicle stimulating hormone(FSH),luteinizing hormone(HLH),pro-gesterone(P),prolactin(PRL)] before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RE-SULTS:The total effective rate in Shengjing capsule group was significantly higher than Jinkui shenqi pill group,with statistical significance(P0.05). After treatment,semen quality in 2 groups was significantly higher than before,semen volume and sperm motility in Shengjing cap-sule group were higher than Jinkui shenqi pill group,with statistical significances(P0.05). And there was no significant difference in the incidence of adverse reactions(P>0.05). CONCLUSIONS:Under behavioral interven-tion,Shengjing capsule has better efficacy than Jinkui shenqi pill in the treatment of oligoasthenozoosperimia,it can significantly improve semen quality,while Jinkui shenqi pill is better in terms of improving sex hormone levels;and both show good safety.

Influence of Kidney- yang Warming Therapy on Expression of Th_1/Th_2 Cytokines in Rats with Allergic Rhinitis / 中药新药与临床药理

Objective To find out the relationship between kidney- yang- deficiency syndrome and the Th1/Th2 expression, and to investigate the effect of kidney- yang warming therap yon the Th1/Th2 expression. Methods Kidney- yang- deficiency rat models were firstly induced by adenine and then were sensitizated by inhalation of ovalbumin to establish allergic rhinitis (AR)models .The treatment group was given Jinkui Shenqi pill. After treatment , the changes of behavior , secretion of nasal cavity and nasal mucosa were observed. The levels of Th1 cytokines IFN- ? , IL- 2 and Th2 cytokines IL- 4 , IL- 5 in serum were determined by ELISA. Results The behavioral score in AR group and kidney- yang- deficiency AR group was higher than that in the treatment group and normal control group ( P

Pharmacokinetics of effective constituent in Jinkui Shenqi Pill / 中成药

AIM:To investigate pharmacokinetics of cinnamon acid and paeonol in Jinkui Shenqi Pill(Radix Rehmanniae Praeparata,Cortex Cinnamomi,Radix Aconiti Lateralis praeparata,Rhizoma Alismatis,etc.)in rabbit.METHODS:RP-HPLC was used to examine blood concentration of cinnamon acid and paeonol in rabbit which was administred Jinkui Shenqi Pill.Chromatographic condition consisted of Symmetry C_ 18(5?m,3.9 mm ?150 mm)chromato graphic column,mobile phase(methanol-1%glacial acetic acid water-solution(45∶55)),flow rate(0.8 mL/min),column temperature(35 ℃),detection wavelength of cinnamon acid(285 nm),detection wave length of paeonol(274 nm).The serum pharmacokinetic parameters were calculated with 3p87 program.RESULTS:Linear range of cinnamon acid ranged from 0.06 ?g/mL to 15 ?g/mL(r=0.999 7),the lowest detectability was 0.054 ?g/mL.Pharmacokinetic process of paeonol in rabbit could be fitted to two-compartment model;Linear range of paeonol ranged from 0.2 ?g/mL to 10 ?g/mL(r=0.999 9),the lowest detectability was 0.02 ?g/mL.Pharmacokinetic process of cinnamon acid in rabbit could be fitted to one-compartment model.CONCLUSION:HPLC detection of serum concentration of cinnamon acid and paeonol is simple,rapid,highly accurate and sensitive.Pharmacokinetic parameters can reveal pharmacokinetics of cinnamon acid and paeonol of Jinkui Shenqi Pill in rabbit.