Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Clinical efficacy of Baijin pills in the treatment of generalized tonicclonic seizure epilepsy with cognitive impairment

BACKGROUND The generalized tonic-clonic seizure(GTCS)is the most usual variety of epileptic seizure.It is mainly characterized by strong body muscle rigidity,loss of consciousness,a disorder of plant neurofunction,and significant damage to cognitive function.The effect of antiepileptic drugs on cognition should also be considered.At present,there is no effective treatment for patients with epilepsy,but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should,therefore,be considered for the therapy means of epilepsy with cognitive dysfunction.AIM To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment.METHODS This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups(experimental and control)using random number table method.The control group was treated with sodium valproate,and the experimental group was Baijin pills and sodium valproate for three months.The frequency and duration of each seizure,the Montreal Cognitive Assessment Scale(MoCA),and the Quality of Life Rating Scale(QOLIE-31)were recorded before and after treatment.RESULTS There were 85 patients included(42 in the control group and 43 in the experimental group).After treatment,the seizure frequency in the experimental group was significantly reduced(P<0.05),and seizure duration was shortened(P<0.01).The total MoCA score in the experimental group significantly increased compared to before treatment(P<0.01),and the sub-item scores,except naming and abstract generalization ability,significantly increased(P<0.05),whereas the total MoCA score in the control group significantly decreased after treatment(P<0.05).The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment(P<0.01).CONCLUSION Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.

Effect of dietary with Zhibai dihuang pills and gonadotropinreleasing-hormone-analogue on girls with precocious and rapidly progressive puberty

BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.

Effects of Fufang Biejia Ruangan Pills on hepatic fibrosis in vivo and in vitro

AIM:To explore the protective effect and the relevant mechanisms of Fufang Biejia Ruangan Pills(FFBJRGP)on hepatic fibrosis in vivo and in vitro.METHODS:Hepatic fibrosis was induced by carbon tetrachloride composite factors.Adult Wistar rats were randomly divided into four groups:normal control group;hepatic fibrosis model group;FFBJRGP-treated group at a daily dose of 0.55 g/kg;and colchicinetreated group at a daily dose of 0.1 g/kg.The effects of FFBJRGP on liver function,serum levels of hyaluronic acid(HA),typeⅣcollagen(CⅣ),typeⅢprocollagen(PCⅢ),laminin(LN),histopathology,and expression of transforming growth factor(TGF-β1)and Smad3 in hepatic fibrosis were evaluated in vivo.The effects of FFBJRGP on survival rate,hydroxyproline content and cell cycle distribution were further detected in vitro.RESULTS:Compared with the hepatic fibrosis model group,rats treated with FFBJRGP showed a reduction in hepatic collagen deposition and improvement in hepatic lesions.Compared with those of the model group,the activities of alanine aminotransferase(62.0±23.7 U/L)and aspartate aminotransferase(98.8±40.0 U/L)in the FFBJRGP-treated group were decreased(50.02±3.7 U/L and 57.2±30.0 U/L,respectively,P<0.01).Compared with those in the model group,the levels of PCⅢ(35.73±17.90 g/mL),HA(563.82±335.54 ng/mL),LN(89.57±7.59 ng/mL)and CⅣ(29.20±6.17ng/mL)were decreased to 30.18±9.41,456.18±410.83,85.46±7.51 and 28.02±9.45 ng/mL,respectively.Reverse-transcriptase polymerase chain reaction and Western blotting also revealed that expression of TGF-β1 and Smad3 were down-regulated in vivo.Cell proliferation was inhibited,the level of hydroxyproline was decreased compared with the control group(P<0.01),and the cell cycle was redistributed when exposed to FFBJRGP in vitro.CONCLUSION:FFBJRGP inhibits hepatic fibrosis in vivo and in vitro,which is probably associated with downregulation of fibrogenic signal transduction of the TGF-β-Smad pathway.

Clinical and experimental study of therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions

IMS To observe the therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions.METHODS Thirty patients with gastric precancerous lesions were treated with Weixibaonizhuan pills for 3 months. Of the 36 cases, 13 (361%) were mild atrophic gastritis, 14 (389%) moderate atrophic gastritis and 9 (250%) severe atrophic gastritis; among them 22 (611%) and 27 cases (750%) were accompanied with intestinal metaplasia (IM) and dysplasia (DYS) respectively. Of the 36 patients, 20 were men and 16 women, aged from 30-60 years and those aged 30-59 years accounted for 611%. The course of disease ranged from 3 months to 21 years, and 20 (556%) of them had a course of 5-10 years. The clinical manifestations were fullness of the abdomen (31 cases), abdominalgia (27 cases), anorexia (30 cases), gas eructation (26 cases), acid regurgitation (6 cases) and loose stool (9 cases). When treatment ended, the improvement of patients′ clinical symptoms, atrophy of gastric mucosa, IM and DYS were analysed.RESULTS After 3 months′ treatment with Weixibaonizhuan pills, 7 cases recovered, 11 cases were much improved, 13 cases showed some improvement, and 5 cases were ineffective; the total rate of symptomatic improvement was 861%. Of the 13 cases with mild atrophic gastritis, 11 cases changed into superficial gastritis, and 2 cases had no changes. Of the 14 cases of moderate atrophic gastritis, 4 cases changed into superficial gastritis, 7 cases changed into mild atrophic gastritis, and 3 cases had no changes. Five of 9 cases of severe atrophic gastritis were reduced to moderate atrophic gastritis, and 4 cases had no changes. The total effective rate was 778% in chronic atrophic gastritis. Of the 9 cases with mild IM, IM disappeared in 6 cases and 3 showed no change. Of the 10 cases with moderate IM, it disappeared in 2 cases, 5 cases changed to mild IM, and 3 cases had no change. One of the 4 cases of severe IM changed to moderate IM and 3 had no change. The total effective rate was 636% in IM. Of the 16 cases of mild DYS, 11 cases showed disappearance of DYS and 5 had no change. In 9 cases of moderate DYS, 2 showed disappearance, 5 changed to mild DYS and 2 had no change. Two cases of severe DYS, both showed no change. The total effective rate was 667% in DYS. Before treatment, the Ⅰ, Ⅱ, Ⅲ and Ⅳ degree positive expressions of CEA were present in 13, 12, 9 and 2 cases, respectively, whereas after treatment, the positive expressions were present in 25, 7, 3 and 1, respectively. Before treatment, the Ⅰ, Ⅱ, Ⅲ and Ⅳ degree positive expressions of PCNA were present in 16, 11, 10 and 4 respectively, but after treatment, they were present in 21, 9, 5 and 1 respectively. In short, the positive expressions of CEA and PCNA of gastric mucosa were significantly decreased after treatment (P<001).CONCLUSION Weixibaonizhuan pill has a therapeutic effect in gastric precancerous lesions..

Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

Zuogui pills for myelinolysis in a rat model of experimental autoimmune encephalomyelitis

Zuogui pills have been shown to attenuate the inflammatory reaction in a rat model of experimental autoimmune encephalomyelitis （EAE）. The present study attempted to investigate the pathology underlying the influence of Zuogui pills on myelinolysis in EAE rats. Hematoxylin-eosin and Luxol fast blue staining showed that the myelinolysis foci in the cerebrum, cerebellum, brain stem, and the spinal cord of EAE rats were significantly decreased, along with serum myelin basic protein content following treatment with Zuogui pills.

Effect of Shoutai Pills on Th1/Th2 Cytokines in Serum and Endometrium of Rats with Stimulated Ovulation

In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism is not clear.This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism.The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(HCG).Then the rats were randomly divided into model group(M),Shoutai pills group(S),progesterone group(P)and normal group(N).All the pregnant rats were treated from the first day.The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively,and N and M groups were given the same volume of normal saline and distilled water respectively.After treatment for 7 days,the animals were executed for serum and uterine tissues.The ELISA method was adopted to detect the contents of Thl cytokines[interferon-γ(INF-γ),interleukin-2(IL-2)]and Th2 cytokines(IL-4,IL-6,IL-10).The expression of leukemia inhibitory factor(L1F)and leukemia inhibitory factor receptor(LIFR)was detected by Western blotting and real-time PCR.As compared with N group,the expression levels of IFN-y and IL-2 in M group were significantly increased,and those of IL-4,IL-6,IL-10.LIF and LIFR were significantly decreased(P<0.05).As compared with M group,the levels of IL-4,IL-6,IL-10,LIF and LIFR in S group were significantly increased(P<0.05),and those of IFN-γand IL-2 were significantly decreased(P<0.05).It was suggested that Shoutai pills can increase the levels of IL-4.1L-6,IL-10,LIF and LIFR as well as reduce the levels of INF-γand IL-2 in rats with stimulated ovulation.The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balanee of Th1/Th2 cytokines.

Shuyu pills inhibit immune escape and enhance chemosensitization in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is characterized by dysregulation of the immune microenvironment and the development of chemoresistance.Specifically,expression of the programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1)axis,an immune checkpoint,may lead to tumour immune escape,resulting in disease progression.The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha(HIF-1α),and simultaneous inhibition of HIF-1αand PD-L1 has the potential to enhance the host’s antitumour immunity.Moreover,inhibition of the PD-1/PD-L1 axis may mitigate tumour chemoresistance.Shuyu pills(SYPs)contain immunity-enhancing and antitumour components,making them a potential HCC treatment.AIM To investigate the efficacy of SYPs for HCC treatment via simultaneous HIF-1α and PD-L1 inhibition and the mechanism involved.METHODS A subcutaneous xenograft tumour model was first established in BALB/c nude mice by the subcutaneous injection of 1×107 SMMC-7721 cells.Male mice(male,5 weeks old;n=24)were then randomly divided into the following four groups(n=6):Control(0.9%normal saline),SYP(200 mg/kg),SYP+cisplatin(DDP)(200 mg/kg+5 mg/kg DDP weekly via intraperitoneal injection),and DDP(5 mg/kg cisplatin weekly via intraperitoneal injection).The dose of saline or SYPs for the indicated mouse groups was 0.2 mL/d via intragastric administration.The tumour volumes and body weights of the mice were measured every 2 d.The mice were euthanized by cervical dislocation after 14 d of continuous treatment,and the xenograft tissues were excised and weighed.Western blot assays were used to measure the protein expression of HIF-1α,PD1,PD-L1,CD4+T cells,and CD8+T cells in HCC tumours from mice.Quantitative reverse transcription polymerase chain reaction was used for real-time quantitative detection of PD-1,PD-L1,and HIF-1α mRNA expression.An immunofluorescence assay was conducted to examine the expression of CD4+T cells and CD8+T cells.RESULTS Compared to mice in the control group,those in the SYP and SYP+DDP groups exhibited reduced tumour volumes and tumour weights.Moreover,the protein and mRNA expression levels of the oncogene HIF1α and that of the negative immunomodulatory factors PD-1 and PD-L1 were decreased in both the SYP and SYP+DDP groups,with the decrease effects being more prominent in the SYP+DDP group than in the SYP group(HIF-1α protein:Control vs SYP,P=0.0129;control vs SYP+DDP,P=0.0004;control vs DDP,P=0.0152,SYP+DDP vs DDP,P=0.0448;HIF-1αmRNA:control vs SYP,P=0.0009;control vs SYP+DDP,P<0.0001;control vs DDP,P=0.0003,SYP vs SYP+DDP,P=0.0192.PD-1 protein:Control vs SYP,P=0.0099;control vs SYP+DDP,P<0.0001,SPY vs SYP+DDP,P=0.0009;SYP+DDP vs DDP,P<0.0001;PD-1 mRNA:control vs SYP,P=0.0002;control vs SYP+DDP,P<0.0001;control vs DDP,P=0.0003,SPY vs SYP+DDP,P=0.0003;SYP+DDP vs DDP,P=0.0002.PD-L1 protein:control vs SYP,P<0.0001;control vs SYP+DDP,P<0.0001;control vs DDP,P<0.0001,SPY vs SYP+DDP,P=0.0040;SYP+DDP vs DDP,P=0.0010;PD-L1 mRNA:Control vs SYP,P<0.0001;control vs SYP+DDP,P<0.0001;control vs DDP,P<0.0001,SPY vs SYP+DDP,P<0.0001;SYP+DDP vs DDP,P=0.0014).Additionally,the quantitative and protein expression levels of CD4+T cells and CD8+T cells were simultaneously upregulated in the SYP+DDP group,whereas only the expression of CD4+T cells was upregulated in the SYP group.(CD4+T cell quantitative:Control vs SYP+DDP,P<0.0001,SYP vs SYP+DDP,P=0.0005;SYP+DDP vs DDP,P=0.0002.CD4+T cell protein:Control vs SYP,P=0.0033;Control vs SYP+DDP,P<0.0001;Control vs DDP,P=0.0021,SYP vs SYP+DDP,P=0.0004;SYP+DDP vs DDP,P=0.0006.Quantitative CD8+T cells:Control vs SYP+DDP,P=0.0013;SYP vs SYP+DDP,P=0.0347;SYP+DDP vs DDP,P=0.0043.CD8+T cell protein:Control vs SYP+DDP,P<0.0001;SYP vs SYP+DDP,P<0.0001;SYP+DDP vs DDP,P<0.0001).Finally,expression of HIF-1αwas positively correlated with that of PD-1/PD-L1 and negatively correlated with the expression of CD4+T cells and CD8+T cells.CONCLUSION SYPs inhibit immune escape and enhance chemosensitization in HCC via simultaneous inhibition of HIF-1α and PD-L1,thus inhibiting the growth of subcutaneous xenograft HCC tumours.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.

Protective Effect and Action Mechanism of Modified Ershiwuwei Songshi Pills on Chronic Liver Injury Induced by CCL4

[Objectives]To study the protective effect of Ershiwuwei Songshi Pills on chronic liver injury induced by carbon tetrachloride(CCL4)in rats before and after the modification conforming to the compatibility theory of Tibetan medicine,and to explore its action mechanism.[Methods]Male Wistar rats were randomly divided into the blank control group,model group,Hugan tablets group(0.490 g/kg),Ershiwuwei Songshi Pills group(0.117 g/kg),and Modified Ershiwuwei Songshi Pills group(removing cinnabaris,Aristolochia contorta,and Aconitum naviculare,0.105 g/kg).Except the blank group,the remaining groups were injected subcutaneously with 20%carbon tetrachloride olive oil solution every 3 d,and modeled for 6 weeks.During this time,intragastrically administered corresponding drugs.Six weeks later,blood was taken from the femoral artery,and the rats were killed through dislocating the cervical spine,the liver was taken,and the content of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)was determined.Then,liver fibrosis indicators tumor necrosis factor-α(TNF-α),nuclear factor-κB(NF-κB),interleukin-6(IL-6)and interleukin-1β(IL-1β)were detected by immunohistochemical method.[Results]Compared with the model group,the pathological map of the liver section showed that liver injury was improved in each administration group.The serum ALT and AST contents in rats of each administration group were significantly reduced(P<0.05),and the protein expressions of NF-κB,TNF-α,IL-1βand IL-6 in liver tissue were also reduced by varying degrees(P<0.05).[Conclusions]Ershiwuwei Songshi Pills and its modification group have a protective effect on liver injury induced by carbon tetrachloride.The modified prescription conforms to the compatibility rules of Tibetan medicine.The mechanism may be related to reducing the damage caused by inflammatory factors through regulating the role of inflammatory signaling pathway.Thus,it can be used as a reference for future optimization proposals.

Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease

Parkinson's disease(PD) is the second most common neurodegenerative disease in the world;however,it lacks effective and safe treatments. Ginkgo biloba dropping pill(GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids.Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment,the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP.These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

The Protective Effect of Compound Danshen Dripping Pills on Oxidative Stress after Retinal Ischemia/Reperfusion Injury in Rats

Objective: To investigate the effect of Compound Danshen Dripping Pills (CDDP) on oxidative stress after ischemia/reperfusion (I/R) injury in the rat retina. Methods: Adult male SD rats were randomly divided into 3 groups: sham (group A), I/R (group B), and I/R plus CDDP (group C). Retinal ischemia/reperfusion injury (RIRI) was introduced by increasing the intraocular pressure (IOP) to 110 mmHg for 60 min via cannulation into the anterior chamber. Right after the insult, CDDP was administered intragastrically (450 mg/kg/d) for 7 days. The levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined on d1 and d7 after the ischemic insult. Results: Following ischemia, the MDA levels in group B and group C were significantly higher than those in group A (p < 0.01). CDDP significantly lowered MDA levels in group C when compared with group B (p < 0.01). The activities of SOD, GSH-Px and CAT were higher in group A than in group B and group C (p < 0.01). CDDP could increase the activities of SOD, GSH-Px and CAT remarkably in group C when compared with group B (p < 0.01). Conclusion: CDDP can protect the retina from I/R injury through reducing oxidative stress, and thus may be a promising method for the treatment of ischemic retinal disorders.

Application of Ji Desheng Snake Pills Combined with Hypertonic Glucose External Application in Treating Drug-Induced Superficial Phlebitis Caused by Parenteral Nutrition

Objective: The efficacy of Ji Desheng snake pills combined with hypertonic glucose external application in treating drug-induced superficial phlebitis caused by parenteral nutrition (PN) is observed. Methods: Fifty-two cases of drug-induced superficial phlebitis after peripheral parenteral nutrition (PPN) were selected, which were randomly divided into experimental group and control group in accordance with the phlebitis grading. In the experimental group, Ji Desheng snake pills were crushed to make a paste with 50% glucose solution, which was then applied to the affected area of phlebitis, the surface was covered with clean gauze, and properly fixed with tape or bandage. The drug was replaced once a day. In the control group, the gauze soaked with 50% magnesium sulfate solution was used, which was applied to the affected part three times a day in wet, and the efficacy was observed respectively on the 1st, 3rd, 5th and 7th days after applying the drug. Results: On the 1st and 3rd days after treatment, the observed effective rate of the experimental group was higher than that of the control group (42.31% vs. 15.38% and 76.92% vs. 46.15%, respectively). The difference was statistically significant (p th and 7th days after treatment, there was no statistical significance with respect to the efficacy between the experimental group and the control group (p > 0.05). Conclusion: The significant efficacy could be found in early stage after drug-induced superficial phlebitis was treated by Ji Desheng snake pills combined with hypertonic glucose external application, which was superior to that of the traditional treatment of wet application by using gauze soaked in 50% magnesium sulfate solution.

Effect of Qishen Yiqi dripping pills combined with trimetazidine on the treatment of chronic heart failure: A meta-analysis

Objective:To systematically evaluate the safety and effectiveness of Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure.Methods:A total of four English and Chinese electronic databases were searched:CNKI,VIP,CBM,PUBMED.Cochrane bias risk tools were used to assess the methodological quality of qualified studies.Meta-analysis was conducted by Review Manager 5.3.A total of 9 articles were included,with a total sample size of 855 cases,443 cases in the observation group and 412 cases in the treatment group.Results:Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure has a total effective rate(RR=1.22,95%CI[1.15-1.30];p<0.00001),LVEF(MD=6.03,95%CI[5.39,6.67],P<0.00001),BNP(MD=-101.87,95%CI[-109.90,-93.83],P<0.00001),E/A(MD=-4.32,95%CI[-5.70,-2.93],P<0.00001),SYP(MD=-10.32,95%CI[-13.32,-7.32],P<0.00001),LVESD(MD=-5.50,95%CI[-6.03,-4.96],P<0.00001),6-MWT(MD=110.13,95%CI[96.89,123.36],P<0.00001)Adverse reactions occurred less frequently and did not affect treatment.Conclusion:This study shows that QYDP combined with TMZ can improve various indicators of CHF patients.However,due to the small sample size and the generally low quality of research,a more rigorous and reasonably designed RCT is needed to confirm these findings.

Integrated UHPLC-MS and network pharmacology to explore the active constituents and pharmacological mechanisms of Shenzao dripping pills against coronary heart disease

Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.

Xihuang pills induce apoptosis in hepatocellular carcinoma by suppressing phosphoinositide 3-kinase/protein kinase- B/mechanistic target of rapamycin pathway

BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract(0.625mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins(e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.

Protective effect of gingerol dropping pills against alcoholic liver injury in mice

OBJECTIVE To prepare gingerol dropping pills and to investigate its protective effect on alcoholic liver injury. METHODS The prescription was selected by orthogonal design method and the effect of the option and ratio of ground substance,the temperature of drug. The hardness,circular degree,the tail formation and the dissolution time were studied. Totally 40 KM mice were randomly divided into control group,model group,gingerol dropping pill group(400 mg·kg^(-1)·d^(-1)) and positive control group(bifendate,150 mg·kg^(-1)·d^(-1)) of 10 mice each. The mice from the model and two drug groups were administrated with liqueur[0.15 mL/(10 g·d)]daily by gavage for 3 weeks,Two hours later,drug group mice were treated corresponding gingerol dropping pill and bifendate. Meanwhile,the control group were gavaged same amount of normal saline. Finally,when the model of acute alcoholic liver injury was established on the 22 stday,Biochemical indicators of ocular blood in mice were observed.We also observed the change of liver morphology. RESULTS Under optimum conditions,we can obtain dropping pills having circular shape,touching with hardness and short dissolution time. Compared with the control group,the levels of alanine transaminase(ALT),glutamic-oxaloacetic transaminase(AST) and malondialdehyde(MDA) in model group were obviously increased(P<0.01),While the activity of Superoxide dismutase(SOD) were decreased. In addition,In model group,mice liver disorders,hepatic lobule fusion,accompanying a large number of patchy sample liver cell vacuoles,various sizes of fat vacuoles appeared in cytoplasm and inflammatory cell infiltration were visible around the central vein. On the contrary,compared with the model group,drug groups attenuated or even reversed hepatic pathological changes. Form gingerol dropping pill group,an increase in hepatic SOD activity and serum ALT and AST activities were found and a significant decrease in hepatic MDA content were also observed(P<0.01). CONCLUSION The prescription of gingerol dropping pills was reasonable,and the preparation process was simple. Gingerol dropping pills can protect liver from alcoholic liver injury to some extend,and the mechanism may be related to its antioxidant effect.

Effect of Bak Foong Pills on the expression of β-amyloid in rat retina with optic nerve transection

AIM:To investigate the effect of Bak Foong Pills(BFP) on the expression of β-amyloid(Aβ) in rats retina with optic nerve transaction,and its roles and possible mechanisms in protecting optic nerve damage.· METHODS:Seventy-two healthy,Sprague-Dawley,adult rats were randomly assigned to three groups:negative control group(control group),optic nerve transection group(model group) and BFP treatment group(BFP group,100μg/mL) followed by establishing optic nerve transection model.The expression of Aβ was measured at 48 hours by Western-blotting.Moreover,the expressions of Bcl-2,Bax and Caspase-3 mRNA were evaluated at 48 hours by reverse transcriptase polymerase chain reaction(RT-PCR).RESULTS:There were significant differences among the control,model and BFP groups in the expression of Aβ(all P <0.01).Aβ expression was significantly higher in the model and BFP groups than that in the control group(P < 0.01),with a more significant reduction in the BFP group than that in the model group(P <0.01).Moreover,there were also significant differences among the three groups in the expressions of Bcl-2/Bax(Bcl-2:anti-apoptotic;Bax:proapoptotic) and Caspase-3 mRNA(proapoptotic)(all P<0.01).Bcl-2/Bax ratio was significantly lower and Caspase-3 mRNA expression was significantly higher in the model and BFP groups than those in the control group(P <0.01),with a significant growing of Bcl-2/Bax and reduction of Caspase-3 in the BFP group than those in the model group(P<0.01).· CONCLUSION:BFP can down-regulate Aβ expression in retina and may inhibit apoptosis and protect optic nerve by enhancing Bcl-2/Bax ratio and inhibiting Caspase-3 pathway.

Mechanism of action of Wuzi Yanzong pill in the treatment of oligoasthenozoospermia in rats determined via serum metabolomics

Objective:To investigate the mechanism of action of Wuzi Yanzong pill(WYP)in rats with oligoasthenozoospermia(OAZ)via metabolomics and to provide a possible basis for improving this WYP-based treatment.Methods:A rat model of OAZ was established by treating male SpragueeDawley rats with glucosides from Tripterygium wilfordii Hook.F.Seventy-two rats were randomly divided into six groups:control,L-carnitine(positive control),model,and low-,medium-,and high-dose WYP groups.Rats in the experimental groups were treated with WYP for 4 weeks.At the end of the treatment period,sperm cell quality(density,motility,and viability)was assessed using a semen analysis system,mitochondrial membrane potential(MMP)was assessed using flow cytometry,and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ.Further,serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment.Results:A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group.WYP-M and WYP-H treatments significantly improved sperm cell density,motility,and viability compared with those in the model group(all P<.05).Compared with the model group,both WYP-M and WYP-H treatments increased MMP values(P=.006 and P=.021 respectively),while there was no significant difference in the L-carnitine group.L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group.Further,44 differential metabolites and four metabolic pathways,especially autophagy pathway,related to OAZ were identified via metabolomics.Conclusions:WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation.These findings can be employed to improve the efficacy of WYP in humans.