Skin pruritus is a core symptom of various dermatological and systemic diseases， and adversely affects the patient’s quality of life. Its occurrence and development are closely associated with dysfunction of the neuro-endocrine-immune （NEI） network. As a benign stress intervention， acupuncture alleviates itching by modulating the NEI network and initiating the body’s intrinsic regulatory mechanisms. Studies have shown that acupuncture has multi-target regulatory effects. At the nervous system level， it can regulate the balance of neurotransmitters and inhibit key signaling pathways such as transient receptor potential vanillic acid subtype 1（TRPV1）， brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. At the endocrine system level， it can correct the function of the hypothalamic-pituitary-adrenal axis and reduce the levels of stress hormones. At the immune system level， it can rebalance cytokines， inhibit mast cell activation and promote skin barrier repair. In the present article， we systematically elucidate the underlying mechanism of acupuncture in treating pruritus through holistic regulation of the NEI network， aiming at providing a reliable theoretical basis for the basic research on acupuncture treatment of cutaneous pruritus.

OBJECTIVE:To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS:According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS:The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION:Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.

Daozhuo massage therapy for chronic prostatitis is an external treatment method that uses pointing, pressing, pushing, and kneading on specific acupoints to dredge meridians, regulate qi, and activate blood circulation. This therapy has a noticeable clinical therapeutic effect on chronic prostatitis, which is the core syndrome type of blood stasis. This article reviews the Traditional Chinese Medicine (TCM) pathogenesis of chronic prostatitis, the historical overview, clinical application, and operational precautions of Daozhuo massage therapy. It also includes a case study to discuss the significant role, effectiveness, and practical application of Daozhuo massage therapy in the clinical diagnosis and treatment of chronic prostatitis.

Ethnopharmacological relevance: Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance.Aim of the study: This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs).Materials and methods: Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image.Results: Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the adminis-tration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The compre-hensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration.Conclusion: Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

IntroductionIschemic stroke has high morbidity, disability and mortality rates. The effective treatments recommended by guideline have considerable limitations due to their strict range of adaptation and narrow time window. Acupuncture is an effective and safe treatment for ischemic stroke, and the mechanism may be related to autophagy. In this systematic review, we aim to summarize and evaluate the evidence of autophagy in acupuncture therapy for animal models of middle cerebral artery occlusion (MCAO).MethodsPublications will be retrieved from the MEDLINE, Embase, Cochrane Library, Web of Science, CNKI, CBM, CVIP and Wanfang databases. We will include animal experimental studies of acupuncture for MCAO, and the control group will receive placebo/sham acupuncture or no treatment after model establishment. Outcome measures must include autophagy and will include neurologic scores and/or infarct size. The Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool will be used to assess the risk of bias. A meta-analysis will be performed if the included studies are sufficiently homogenous. Subgroup analyses will be conducted according to different intervention types and different types of outcomes. Sensitivity analyses will also performed to explore the heterogeneity and to assess the stability of the results. Publication bias will be assessed by funnel plots. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be applied to evaluate the quality of evidence in this systematic review.DiscussionThe results of this study may help to explain autophagy in acupuncture therapy for ischemic stroke. The limitation of this review is that all included studies will be retrieved from Chinese or English medical databases due to language barriers.RegistrationWe registered in PROSPERO on May 31, 2022. (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=329917) (CRD42022329917).

The impact of depression on spermatogenic function and protein expression was investigated by reference to a bioinformatics database for the prediction of key targets and pathways. Experimental validation was performed using a rat model established using the chronic restraint stress method. Organ coefficients and semen parameters were measured. Hematoxylin and eosin (HE) staining was performed to compare testicular tissue between model and control rats. Western blotting and RT–qPCR were conducted to evaluate protein and mRNA expression. As a result, depression and male infertility (MI) were found to share 81 common targets, and the PI3K/Akt/FOXO1 signaling pathway was involved in both conditions. Animal experiments showed testis and epididymis coefficients to be lower in the model group. HE staining showed damage to the seminiferous tubules of model rats. PI3K and p-Akt mRNA and protein were present at lower levels and FOXO1 at higher levels in the model group. Depression led to reduced spermatogenic function in rats and might be associated with differential expression of the PI3K/Akt/FOXO1 signaling pathway.

Hydroxysafflor yellow A (HSYA), a primary active component in Carthami Flos, has been extensively applied in the treatment of cardiometabolic diseases. In this study, a natural deep eutectic solvent composed of glucose and choline chloride with 10% (v/v) of water (90% GCH) was evaluated to enhance the oral absorption of HSYA. Compared with HSYA in water, the relative oral bioavailability of HSYA in 90% GCH was increased to 326.08%. Furthermore, 90% GCH was demonstrated to decrease the mucus viscosity and increase the absorption rate constant of HSYA in the jejunum by 2.95 times. A pharmacodynamic study revealed that HSYA in 90% GCH was more effective in reducing body weight and correcting steatohepatitis and dyslipidemia in high-fat diet-induced obese rats. Serum metabolomics results showed that the correction of serum aromatic amino acid disorder may contribute to the anti-obesity effect of HSYA in 90% GCH. In conclusion, 90% GCH could be a delivery carrier for HSYA against obesity.

Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.

Review question / Objective: To evaluate the efficacy and safety of TraditionalChinese Medicine (TCM) on the treatment of male infertility due to sperm DNA fragmentation (SDF).

BACKGROUND:Myopia are common health problems that people experience in daily life. Pediatric myopia has become a major international public health concern that has a negative impact on physical, mental health of patients, and quality of life. Currently, there is no cure available. Press needle as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of press needle patching on early myopia. There is also a lack of systematic evaluation and analysis of acupoints and thumbtack needle.METHODS:We will electronically search Medline, Embase, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan-Fang Database from their inception to October 2021. In addition, we will manually retrieve other resources including the reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to press needle for the treatment of early myopia will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using afixed effect model or random effect model depend on the heterogeneity test. The total effective rate was the primary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted. Data synthesis will use the risk ratio and the standardized or weighted average difference of continuous data to represent the results.RESULTS:This study will analyze the clinical effective rate, pesudomyopia outcomes, quality of life, improvement of clinical symptoms of pesudomyopia, and validity of thumbtack needle for patients with pesudomyopia.CONCLUSION:This systematic review will provide evidence to judge whether thumbtack needle is an effective intervention for patients with early myopia.SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42021243151.

Abstract Background Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose–response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment. Methods The proposed methodology of integrated dose–response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose–response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM. Results This developed strategy was successfully applied to rhubarb. The dose–response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case. Conclusion An integrated dose–response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.

Abstract Background: Myopia are common health problems that people experience in daily life. Pediatric myopia has become a major international public health concern that has a negative impact on physical, mental health of patients, and quality of life. Currently, there is no cure available. Press needle as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of press needle patching on early myopia. There is also a lack of systematic evaluation and analysis of acupoints and thumbtack needle. Methods: We will electronically search Medline, Embase, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan-Fang Database from their inception to October 2021. In addition, we will manually retrieve other resources including the reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to press needle for the treatment of early myopia will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using afixed effect model or random effect model depend on the heterogeneity test. The total effective rate was the primary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted. Data synthesis will use the risk ratio and the standardized or weighted average difference of continuous data to represent the results. Results: This study will analyze the clinical effective rate, pesudomyopia outcomes, quality of life, improvement of clinical symptoms of pesudomyopia, and validity of thumbtack needle for patients with pesudomyopia. Conclusion: This systematic review will provide evidence to judge whether thumbtack needle is an effective intervention for patients with early myopia. Systematic review registration: PROSPERO, CRD42021243151.

Objective. This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods. We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results. A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion. Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.

Background Studies have shown that diabetes mellitus (DM) has a negative impact on male reproductive function, which may lead to changes in the testis and epididymis and a decline in semen quality. Material/Methods We performed animal experiments with 6 diabetic db/db mice as the model group (group B) and 6 C57BL/6J mice as the control group (group A). After adaptive feeding for 7 days, the sperm quality of each group was measured. Concurrently, the morphology of the mouse testis was observed by hematoxylin-eosin (H&E) staining. The expression of the PI3K, Akt, FoxO1, FasL, IL-6, and Stat3 proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. Results The number of spermatozoa and sperm motility of group A was significantly higher than that of group B (P<0.05). H&E staining of the testicular tissue showed the seminiferous tubules in group B mice were damaged to varying degrees and the seminiferous tubules were sparsely arranged. Compared with those of group A, the expression levels of PI3K, Akt, and Stat3 proteins and mRNAs in group B were significantly lower (P<0.05), while the expression levels of FoxO1, FasL, and IL-6 proteins and mRNAs in group B mice were significantly higher (P<0.05). Conclusions This study demonstrated that DM inhibited the expression of PI3K, Akt, and Stat3 proteins and mRNAs in the FoxO1 pathway and promoted the expression of FoxO1, FasL, and IL-6 proteins and mRNAs, leading to abnormal apoptosis of testicular tissue cells and functional damage, and eventually spermatogenic dysfunction.

CONTEXT:Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE:Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS:Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 μg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS:The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION:ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

Through network pharmacology research, we found that CYP19, CYP17, AR and SRD5A2 were potential targets for lycium chinense-cuscutae semen (LC-CS) treatment of oligoasthenozoospermia. Using in vitro and in vivo experiments, tripterygium glycosides were used to induce spermatogenic dysfunction models in GC-1spg cells and SD male rats, respectively, and LC-CS was used to intervene in a spermatogenic dysfunction model. In vitro, LC-CS could repair the ultrastructure of GC-1spg cells damaged by tripterygium glycosides (TG). Compared with TG group, LC-CS could upregulate protein and mRNA expression of CYP19, CYP17, AR and SRD5A2. In vivo, compared with TG, the body mass, testicular mass and epididymal weights of rats in TG + LC-CS increased. Progressive motility + nonprogressive motility spermatozoon (PR + NP) of TG + LC-CS were upregulate than TG. The levels of FSH, LH and testosterone in TG + LC-CS were upregulate than TG. LC-CS can repair the ultrastructure of spermatogonia damaged by TG (the above results are statistically significant, p <.05). Results of H&E staining and TEM showed that the morphology and ultrastructure of testicular tissue in TG + LC-CS were better than that in TG. Compared with TG, LC-CS could upregulate the expression of CYP19, CYP17, AR and SRD5A2 proteins and mRNA.

Methods: Relevant potential targets for EC were obtained based on Traditional Chinese Medicine System Pharmacology Database (TCMSP), a bioinformatics analysis tool for molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM) and STITCH databases. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were utilized to screen the known POI-related targets, while Cytoscape software was used for network construction and visualization. Then, the Gene Ontology (GO) and pathway enrichment analysis were carried out by the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Furthermore, KGN cells were performed to validate the predicted results in oxidative stress (OS) model, and antioxidant effect was examined. Results: A total of 70 potential common targets for EC in the treatment of POI were obtained through network pharmacology. Metabolic process, response to stimulus and antioxidant activity occupied a leading position of Gene Ontology (GO) enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that PI3K/protein kinase B (AKT), TNF, estrogen, VEGF and MAPK signaling pathways were significantly enriched. In addition, cell experiments showed that EC exhibited antioxidant effects in an H2O2-mediated OS model in ovarian granulosa cells by regulating the expression of PI3K/AKT/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and multiple downstream antioxidant enzymes. Conclusion: EC could regulate multiple signaling pathways and several biological processes (BPs). EC had the ability to down-regulate elevated OS level through the PI3K/AKT/Nrf2 signaling pathway and represented a potential novel treatment for POI.

Background Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. Materials and Methods We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). Results There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). Conclusions The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.

Chronic constipation is a common gastrointestinal disorder, with a worldwide incidence of 14–30%. It negatively affects quality of life and is associated with a considerable economic burden. As a disease with multiple etiologies and risk factors, it is important to understand the pathophysiology of chronic constipation. The purpose of this review is to discuss latest findings on the roles of gut motility, fluid, and electrolyte transport that contribute to chronic constipation, and the main drugs available for treating patients. We conducted searches on PubMed and Google Scholar up to 9 February 2021. MeSH keywords “constipation”, “gastrointestinal motility”, “peristalsis”, “electrolytes”, “fluid”, “aquaporins”, and “medicine” were included. The reference lists of searched articles were reviewed to identify further eligible articles. Studies focusing on opioid-induced constipation, evaluation, and clinic management of constipation were excluded. The occurrence of constipation is inherently connected to disorders of gut motility as well as fluid and electrolyte transport, which involve the nervous system, endocrine signaling, the gastrointestinal microbiota, ion channels, and aquaporins. The mechanisms of action and application of the main drugs are summarized; a better understanding of ion channels and aquaporins may be helpful for new drug development. This review aims to provide a scientific basis that can guide future research on the etiology and treatment of constipation.

Ethnopharmacological relevance: Semen Cuscutae is the seed of Cuscuta japonica Choisy, and Fructus Lycii is the mature fruit of Lycium barbarum L. (Solanaceae). Semen Cuscutae and Fructus Lycii (SC-FL) are well-known Chinese medicine which have been used to tonify the kidney and replenish the essence for thousands of years. Chinese physicians prefer to prescribe them for treating male infertility. Recent studies have found that SC-FL repair spermatogenic dysfunction, however, the therapeutic mechanism has yet to be clearly elucidated. Aim of the study: This study aimed at evaluating the therapeutic effect of SC-FL in glucosides of Tripterygium wilfordii Hook. f (GTW)-induced dyszoospermia rats and elucidating the underlying molecular mechanism. Materials and methods: Seventy-eight Sprague-Dauley (SD) rats were randomly divided into five groups: normal control (treated with saline), GTW (treated with saline), GTW + levocarnitine (treated with levocarnitine), GTW + SCFL (treated with SC-FL), and LY (LY294002, the PI3K inhibitor) +SCFL (treated with SC-FL). GTW (40 mg/kg/d) was intragastrically administered for 4 weeks to establish dyszoospermia model. From the start of the study, LY was additionally injected into the tail vein of rats of the LY + SCFL group once a week. After 8 weeks, semen quality and organ coefficient were determined and sex hormone, inhibin B, and epididymal carnitine levels were measured. Testicular tissue and its ultrastructure were observed using H&E (hematoxylin-eosin) staining and electron microscopy. Immunohistochemistry, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to determine the protein and mRNA expression of SCF, c-kit, PI3K, p-Akt, Bad, Bcl-2, and Bax in rat testis. Results: Compared with the GTW group, semen quality, the organ coefficient, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and epididymal carnitine levels were significantly improved in the GTW + SCFL group (P < 0.05 or P < 0.01). Histomorphology and testicular ultrastructural evaluation showed that in the GTW + SCFL group, the structure and arrangement of seminiferous tubules were better, the amount of spermatogenic cells increased significantly, the morphology of spermatogenic cells improved, and the mitochondria increased, compared to those in the GTW group. Immunohistochemistry, western blotting, and qRT-PCR results showed that compared with the GTW group, the expression of SCF, c-kit, PI3K, p-Akt, and Bcl-2 in the GTW + SCFL group was increased, while that of Bax and Bad was decreased. The expression of p-Akt and Bcl-2 decreased, while that of Bad and Bax increased in the LY + SCFL group compared with the SCFL group. Conclusion: SC-FL can effectively inhibit spermatogenic cell apoptosis and promote their proliferation, and the mechanism may be related to the regulation of the SCF/c-kit-PI3K-Bcl-2 pathway.