Phoenix dactylifera L. pollen versus pentoxifylline on improvement of sperm parameters in idiopathic male infertility: A randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. pollen is the male reproductive dust of palm flowers known as a natural product that is considered a strong stimulant of sexual potency and fertility in Iranian traditional medicine (ITM). In this regard, no evidence-based medications are empirically prescribed to treat IMI. However, applying traditional medicine for the treatment of male infertility has attracted more attention in recent years. AIM OF THE STUDY: Phoenix dactylifera L. pollen was compared with pentoxifylline (PTX) to evaluate its efficacy on sperm parameters. MATERIALS AND METHODS: During this parallel randomized controlled trial, 80 adult men with asthenozoospermia, oligozoospermia, or teratozoospermia (age 20-35 years) were enrolled. In two separate groups of participants with a 1:1 ratio, participants received either 6 g of Phoenix dactylifera L. pollen powder daily or 400 mg of PTX tablets daily for 90 days. We measured the sperm parameters as well as the serum sex hormones in the sample. ANCOVA and t-tests were used to compare groups. RESULTS: There was no significant difference between the study groups in terms of baseline characteristics or demographic characteristics. According to the results, participants who took Phoenix dactylifera L. pollen powder had significantly improved sperm concentration (p = 0.016), morphology (p = 0.029), sperm counts (p = 0.012), progressive motility (p = 0.016), total motility (p = 0.018), and reduced immotile sperms (p = 0.014) compared to those who took PTX. CONCLUSIONS: In light of these results, Phoenix dactylifera L. pollen is recommended as a treatment factor for ameliorating IMI by enhancing sperm functional capacity and semen parameters.

Ursonic acid attenuates spermatogenesis in oligozoospermia mice through inhibiting ferroptosis.

Ursonic acid (UNA) is a natural pentacyclic triterpene found in some medicinal plants and foods. The reproductive protective effect of UNA was evaluated in a mouse model of oligozoospermia induced by busulfan (BUS) at 30 mg/kg b.w.. The mice were initially divided into groups with UNA concentrations of 10, 30, 50, 100 mg/kg. Subsequently, based on sperm parameters, the optimal concentration of 50 mg/kg was identified. As a control, an additional group was supplemented with ursolic acid at a concentration of 50 mg/kg. The results indicated that BUS caused the loss of spermatogenic cells in testis, the decrease of sperm in epididymis, the disorder of testicular cytoskeleton, the decrease of serum sex hormones such as testosterone which induced an increase in feedback of androgen receptor and other testosterone-related proteins, the increase of malondialdehyde and reactive oxygen species levels and the increase of ferroptosis in testis while UNA successfully reversed these injuries. High-throughput sequencing revealed that UNA administration significantly upregulated the expression of genes associated with spermatogenesis, such as Tnp1, Tnp2, Prm1, among others. These proteins are crucial in the histone to protamine transition during sperm chromatin remodeling. Network pharmacology analysis reveals a close association between UNA and proteins related to the transformation of histones to protamine. Molecular docking studies reveal that UNA can interact with the ferroptosis-inhibiting gene SLC7A11, thereby modulating ferroptosis. Taken together, UNA alleviated BUS-induced oligozoospermia by regulating hormone secretion, mitigating oxidative stress and promoting recovery of spermatogenesis by inhibiting the ferroptosis.

Moxibustion prevents tripterygium glycoside-induced oligoasthenoteratozoospermia in rats via reduced oxidative stress and modulation of the Nrf2/HO-1 signaling pathway.

Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using Western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.

Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue.

ETHNOPHARMACOLOGICAL RELEVANCE: Antler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong's Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei's Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. AIM OF THE STUDY: The Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. MATERIALS AND METHODS: So the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I-V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. RESULTS: Vinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. CONCLUSION: Vinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.

Tong Jing Yi Hao Formula Alleviates Ornidazole-Induced Oligoasthenospermia in Rats by Suppressing ROS/MAPK/HIF-1 Pathway.

BACKGROUND: Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem. METHODS: Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway. RESULTS: Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde. In the testicles, an enhancement in the ROS level and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) was observed after Orn challenge. Moreover, the protein expression levels and immunostaining intensity of p38 and HIF-1α increased, indicating the activation of the ROS/MAPK/HIF-1 pathway. All of the aforementioned changes exhibited statistical significance (p < 0.01). Compared with Orn-induced rats, TJYHF effectively rescued the Orn-induced aforementioned disorders. Mechanistically, TJYHF suppressed the ROS level and ERK1/2, JNK and p38 phosphorylation levels. Besides, it reduced the protein expression levels and immunostaining intensity of p38 and HIF-1α, demonstrating the inactivation of the ROS/MAPK/HIF-1 pathway. Notably, the aforementioned enhancements demonstrated statistical significance (p < 0.01). CONCLUSIONS: TJYHF exerted a beneficial effect on reproductive function in OAS rats through the inhibition of the ROS/MAPK/HIF-1 pathway.

[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.

Protective Effects of Chia Seeds and Omega-3 Fatty Acid against Cyclophosphamide-Induced Oligospermia in Male Wistar Rats: Potential Risks of Adverse Drug Interaction with Chia Seeds.

Objectives: The aim of this study was to investigate whether chia (Salvia hispanica) seeds, which are rich in omega-3 fatty acids, amino acids, and vitamins with antioxidant properties, can mitigate the negative effects on male reproductive function caused by cyclophosphamide, a frequently used chemotherapeutic agent. Methods: Male wistar rats are divided into seven groups (n=6). All groups except the normal control (NC) received cyclophosphamide (30mg/kg, i.p.) for the first 5 days. The standard group received clomiphene citrate (0.25 mg/kg, p.o.). Treatment groups T1%, T5%, T10%, and ω-3 received 1%, 5%, and 10% chia seeds in the diet, and 880 mg/kg omega-3 fatty acid (p.o) respectively for 15 days. The effect on the reproductive system was evaluated by analysis of epididymal sperm characteristics, biochemical parameters, and serum testosterone level. Results: Clomiphene citrate improved oligospermia via hormone mediated effect. Chia seeds and omega-3 fatty acid treatment also showed improvement in reproductive parameters including oxidative stress and histological features of the testes. Omega-3 fatty acid treatment was more effective for the prevention of cyclophosphamide toxicity on testes as compared to chia seeds. Nasal bleeding was noted in several animals subjected to chia seed treatment. This occurrence might be attributed to chia seeds' impact on coagulation and/or platelet function, potentially heightened due to chemotherapy associated bone marrow suppression. Conclusions: In our study, chia seeds as well as omega-3 fatty acid treatment were found to be protective against cyclophosphamide-induced reproductive toxicity in rats. However, the adverse effect of hemorrhage associated with drug interaction of chia seeds with cytotoxic chemotherapeutic drugs needs careful attention and further investigation.

Improvement of Astragalin on Spermatogenesis in Oligoasthenozoospermia Mouse Induced by Cyclophosphamide.

More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.

[L-carnitine-astaxanthin compound nutrients for the treatment of idiopathic oligospermia and asthenozoospermia: A multicenter clinical observation].

OBJECTIVE: To investigate the clinical effects of the L-carnitine-astaxanthin compound nutrients Menglankang (MLK) on idiopathic oligospermia (OS) and asthenospermia (AS). METHODS: This study included 73 cases of OS and 220 cases of AS treated with MLK once a bag, bid, for 3 successive months. Before and at 1, 2 and 3 months after treatment, we obtained and analyzed the semen parameters and sperm DNA fragmentation index (DFI) of the patients. RESULTS: Compared with the baseline, the OS patients showed remarkable increases after 1 and 2 months of treatment in the semen volume (ï¼»3.07 ± 1.47ï¼½ vs ï¼»3.26 ± 1.26ï¼½ and ï¼»3.30 ± 1.28ï¼½ ml), sperm concentration (ï¼»10.96 ± 6.09ï¼½ vs ï¼»16.74 ± 11.15ï¼½ and ï¼»17.56 ± 9.92ï¼½ ×106/ml, P < 0.05), total sperm count (ï¼»29.78 ± 17.48ï¼½ vs ï¼»52.98 ± 32.07ï¼½ and ï¼»57.67 ± 36.98ï¼½ ×106, P < 0.05) and the percentages of progressively motile sperm (PMS) (ï¼»39.8 ± 11.66ï¼½% vs ï¼»45.3 ± 14.03ï¼½% and ï¼»46.42 ± 10.69ï¼½%, P < 0.05) and morphologically normal sperm (MNS) (ï¼»1.71 ± 1.07ï¼½% vs ï¼»1.79 ± 0.91ï¼½% and ï¼»1.84 ± 0.96ï¼½%), and so did the AS patients in PMS (ï¼»19.23 ± 8.32ï¼½% vs ï¼»25.46 ± 13.86ï¼½% and ï¼»27.33 ± 12.88ï¼½%, P < 0.05). After 3 months of medication, the OS patients exhibited even more significant increases in the semen volume (ï¼»3.63 ± 1.39ï¼½ ml) (P < 0.05), sperm concentration (ï¼»20.56 ± 14.7ï¼½ ×106/ml) (P < 0.05), total sperm count (ï¼»66.35 ± 55.91ï¼½ ×106) (P < 0.05), PMS (ï¼»49.24 ± 13.45ï¼½%) (P < 0.05) and MNS (ï¼»2.59 ± 0.93ï¼½%) (P < 0.05), and so did the AS patients in the semen volume (ï¼»3.27 ± 1.42ï¼½ vs ï¼»3.85 ± 1.59ï¼½ ml, P < 0.05), PMS (ï¼»29.11 ± 13.58ï¼½%) (P < 0.05) and NMS (ï¼»2.01 ± 1.14ï¼½% vs ï¼»2.57 ± 1.15ï¼½%, P < 0.05). In comparison with the baseline, the sperm DFI was not significantly improved at 1 month after treatment, but remarkably decreased at 2 and 3 months in the OS patients (ï¼»25.87 ± 13.76ï¼½% vs ï¼»18.66 ± 10.83ï¼½% and ï¼»16.48 ± 11.46ï¼½%, P < 0.05) and the AS patients as well (ï¼»26.40 ± 12.28ï¼½% vs ï¼»19.35 ± 11.54ï¼½% and ï¼»15.32 ± 10.89ï¼½%, P < 0.05). CONCLUSIONS: The L-carnitine-astaxanthin compound nutrients Menglankang can significantly improve the semen quality of the patients with idiopathic oligospermia or asthenospermia.

Runjing extract promotes spermatogenesis in rats with ornidazole-induced oligoasthenoteratozoospermia through extracellular signal-regulated kinase signalling, and regulating vimentin expression.

OBJECTIVE: To investigate the efficacy of Runjing (RJ) extract on oligoasthenoteratozoospermia (OAT) induced by ornidazole (ORN) in rats, and to study the underlying mechanism. METHODS: Twenty-four adult male Sprague-Dawley rats were treated with normal saline (control), ORN (OAT model), ORN + 4.725 g·kg－1·d－1 RJ extract (low-dose) and ORN+ 18.9 g·kg－1·d－1 RJ extract (high-dose) for 4 weeks. The rats were then euthanized and sperm and testis samples were collected for analysis. Sperm count, motility and morphology were calculated by sperm suspension from cauda epididymis. Testicular histopathological changes were analyzed by hematoxylin and eosin staining and TdT mediated dUTP nick end labelling. Moreover, the expression of vimentin and extracellular signal-regulated kinase (ERK) were examined through Western blot, and the distribution of vimentin was detected via immunohistochemistry. RESULTS: ORN successfully induces seminiferous epithelium injury, cellular apoptosis, and finally OAT (P < 0.05). However, both low-dose and highdose RJ extract partially rescues the phenotypes (P < 0.05). Moreover, the expressions of vimentin and ERK were significantly altered in ORN testes (all P < 0.001), while RJ extract partially reversed these effects (P < 0.01 or P < 0.001). CONCLUSION: RJ extract can help maintain spermatogenesis through ERK signalling, and regulating vimentin expression.

A network pharmacology approach to determine the underlying mechanisms of action of Yishen Tongluo formula for the treatment of oligoasthenozoospermia.

Oligoasthenozoospermia is a complex disease caused by a variety of factors, and its incidence is increasing yearly worldwide. Yishen Tongluo formula (YSTLF), created by Professor Sun Zixue, has been used to treat oligoasthenozoospermia in clinical practice for several decades with a good therapeutic effect. However, the chemical and pharmacological profiles of YSTLF remain unclear and need to be elucidated. In this study, a network pharmacology approach was applied to explore the potential mechanisms of YSTLF in oligoasthenozoospermia treatment. All of the compounds in YSTLF were retrieved from the corresponding databases, and the bioactive ingredients were screened according to their oral bioavailability (OB) and drug-likeness (DL). The potential proteins of YSTLF were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, while the potential genes of oligoasthenozoospermia were obtained from the GeneCards database and the DisGeNET database. The STRING database was used to construct an interaction network according to the common targets identified by the online tool Venny for YSTLF and oligoasthenozoospermia. The topological characteristics of nodes were visualized and analyzed through Cytoscape. Biological functions and significant pathways were determined and analyzed using the Gene Ontology (GO) knowledgebase, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Metascape. Finally, the disease-formula-compound-target-pathway network was constructed by Cytoscape. A total of 106 bioactive ingredients and 134 potential targets from YSTLF were associated with oligoasthenozoospermia or considered to be therapeutically relevant. Pathway analysis indicated that the PI3K/Akt, MAPK and apoptosis signaling pathways were significant pathways involved in oligoasthenozoospermia. In conclusion, the current study expounded the pharmacological actions and molecular mechanisms of YSTLF in treating oligoasthenozoospermia from a holistic viewpoint. The potential molecular mechanisms were closely related to antioxidative stress, antiapoptosis and anti-inflammation, with TNF, CCND1, ESR1, NFKBIA, NR3C1, MAPK8, and IL6 being possible targets. This network pharmacology prediction may offer a helpful tool to illustrate the molecular mechanisms of the Chinese herbal compound YSTLF in oligoasthenozoospermia treatment.

[Clinical observation of herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS for asthenospermia and oligospermia].

OBJECTIVE: To observe the clinical effect of herb-separated moxibustion on segmental conception vessel combined with low-frequency transcutaneous electrical acupoint stimulation (TEAS) for asthenospermia and oligospermia. METHODS: A total of 105 patients with asthenospermia and oligospermia were randomly divided into a combination group, a TEAS group and a medication group, 35 cases in each one. In the medication group, vitamin E capsules, coenzyme Q10 capsules，Wuzi Yanzong pills were taken. In the TEAS group, TEAS was applied at Shenshu (BL 23) and Pishu (BL 20), 2 Hz in frequency, 10-15 mA in intensity, once every 2 days, 30 min each time.On the base of the treatment as the TEAS group, herb-separated moxibustion on segmental conception vessel [Shenque (CV 8) to Zhongji (CV 3)] was applied in the combination group, once every 10 days. A total of 3 months were required in the 3 groups.Before treatment and 2, 3 months into treatment, the semen routine indexes (concentration, normal morphology rate, sperm motility), seminal plasma contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and TCM syndrome score were observed in the 3 groups, and the clinical efficacy was evaluated. RESULTS: Compared before treatment, except for the sperm morphology 2 months into treatment in the medication group, the semen routine indexes 2, 3 months into treatment were improved in the 3 groups (P<0.01), and the semen routine indexes 2, 3 months into treatment in the combination group were superior to the medication group and the TEAS group (P<0.01). Compared before treatment, the seminal plasma contents of SOD were increased and MDA were decreased 2, 3 months into treatment in the 3 groups (P<0.01), and the changes of the combination group were larger than the medication group and the TEAS group (P<0.01). Compared before treatment, the TCM syndrome scores 2, 3 months into treatment in the combination group, and 3 months into treatment in the medication group and the TEAS group were decreased (P<0.01). The TCM syndrome scores 2, 3 months into treatment in the combination group were lower than the medication group and the TEAS group (P<0.01). The total effective rates in the combination group, the medication group and the TEAS group were 85.7% (30/35), 68.6% (24/35) and 65.7% (23/35), the clinical efficacy of the combination group was higher than the medication group and the TEAS group (P<0.05). CONCLUSION: Herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS can improve semen routine, reduce sperm oxidative stress damage for patients with asthenospermia and oligospermia, and the clinical efficacy is better than the medication and TEAS.

Comparing the pharmacokinetics of 13α,21-dihydroeurycomanone and eurycomanone exclusively enriched in Eurycoma longifolia extracts and their spermatogenesis enhancement in andrographolide-induced oligospermia in rats.

OBJECTIVES: The quassinoids eurycomanone (EN) and 13α,21-dihydroeurycomanone (DHY) of Eurycoma longifolia Jack are reported to enhance spermatogenesis. This study aims to profile the pharmacokinetics of DHY, a minor and hitherto unstudied constituent, evaluate its spermatogenesis enhancement property and compare these attributes with that of the predominant EN. METHODS: Crude Eurycoma longifolia extract was chromatographed into a DHY-enriched extract (DHY-F) and an EN-enriched extract (EN-F). Male Sprague-Dawley rats were administered intravenously and orally with both extracts and their plasma levels of both quassinoids were determined. The extracts were then tested for their spermatogenesis augmentation ability in normal rats and an andrographolide-induced oligospermia model. KEY FINDINGS: Chromatographic enrichment resulted in a 28-fold increase of DHY in DHY-F and a 5-fold increase of EN in EN-F compared with non-chromatographed crude extracts. DHY showed better oral bioavailability (1.04 ± 0.58%) than EN (0.31 ± 0.19%). At 5 mg/kg, EN exhibited higher efficacy in spermatogenesis enhancement in normal rats and restoration of oligospermia to normal sperm profile versus DHY. CONCLUSIONS: Despite the better pharmacokinetic profile of DHY, EN remains the main chemical contributor to plant bioactivity. DHY-F and EN-F represent improvements in developing Eurycoma longifolia as a potential phytomedicine for male infertility particularly oligospermia.

Improvement of Qilin pills on male reproductive function in tripterygium glycoside-induced oligoasthenospermia in rats.

This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups: (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg-1  d-1 ) and high dose (3.24 g kg-1  d-1 ) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p < .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p < .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p < .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.

NMR-based metabolomics approach to study the effects of Wu-Zi-Yan-Zong-Wan on triptolide-induced oligospermia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Zi-Yan-Zong-Wan (WZYZW) is a commonly used Chinese medicinal recipe for oligozoospermia. Oligozoospermia is a common disease that harms human fertility, there is no effective therapeutic medicine at present. However, the underlying pharmacological mechanism remains unclear. METHODS: Oligozoospermia rats model induced by Tripterygium glycosides (TG) was established to inspect the efficiency of WZYZW in the treatment of oligozoospermia by traditional pharmacodynamics combined with NMR-based metabolomics. Multivariate statistics were used to extracted the underlying biomarkers and metabolic pathways of WZYZW in the treatment of oligozoospermia. RESULTS: The results showed that TG disturbed many metabolites and metabolic pathways such as oxidative stress (choline, O-phosphocholine, betaine and ascorbate), energy metabolism in mitochondria (glucose, lactate, succinate, fumarate, 3-hydroxybutyrate and alanine), mitochondrial apoptosis markers (Bax and Bcl-2) and amino acids metabolisms (arginine, branched-chain amino acids, taurine and myo-inositol). CONCLUSIONS: WZYZW could significantly reverse the disturbed metabolites to their normal status by their abilities of anti-oxidation, anti-apoptosis, balancing the osmotic pressure regulatory molecules and regulating the amino acids metabolism. This study provides pharmacological basis and guidance for the clinical usage of WZYZW.

Acupuncture for oligospermia and asthenozoospermia: A systematic review and meta-analysis.

BACKGROUND: Acupuncture is widely used for oligospermia and asthenozoospermia in China, but its effect is unclear. We aimed to determine the effectiveness and safety of acupuncture in treating oligospermia and asthenozoospermia. METHODS: An electronic search for randomized controlled trials evaluating acupuncture treatment in patients with oligospermia and asthenozoospermia published from database inception to October 2018 was conducted in PubMed, EMBASE, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database (VIP Database), the Wan-Fang Database, the China National Knowledge Infrastructure and the Cochrane Library. We established search terms related to 3 areas (oligospermia, asthenozoospermia, and acupuncture). Two authors independently screened all identified citations and extracted the data. The methodological quality of the included trials was assessed using the Cochrane criteria. RESULTS: Seven studies with a total of 527 subjects were screened according to inclusion and exclusion standards, and most of the studies had significant methodological weaknesses. Seven randomized controlled trials tested the effects of acupuncture compared with placebo acupuncture and conventional medications in patients with oligospermia and asthenozoospermia. The results of this study suggest that acupuncture alone has no clear superiority in improving sperm motility (standard mean difference [SMD] = 1.13, 95% confidence interval [CI]: -0.64 to 2.89), the sperm concentration (SMD = 0.32, 95% CI: 0.27-0.92) or semen volume compared with placebo acupuncture. No significant difference was found between acupuncture alone and conventional medications in improving sperm motility (SMD = -0.53, 95% CI: -2.54 to 1.48), the sperm concentration (SMD = -1.10, 95% CI: -1.48 to -0.72) or semen volume. However, adjuvant acupuncture may enhance the effect of medications on improving sperm motility (SMD = 4.10, 95% CI: 1.09-7.12) and the sperm concentration (SMD = 1.07, 95% CI: 0.739-1.40), but the study heterogeneity was too high to establish robust conclusions. CONCLUSION: These results suggest that the current evidence does not support acupuncture as an effective treatment for oligospermia and asthenozoospermia; therefore, acupuncture is not currently recommended as a treatment for these conditions. However, owing to the high risk of bias among the included studies, the evidence is limited, and more large-scale, high-quality clinical trials are needed in the future. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018083885.

Sperm performance in oligoasthenoteratozoospermic patients is induced by a nutraceuticals mix, containing mainly myo-inositol.

The action of myo-inositol (MI), belonging to the inositol family, has been shown to improve sperm quality. To further elucidate the efficacy of this substance in male fertility, we investigated in vivo the effects of a nutraceuticals mix, containing mainly myo-inositol (MI) and in vitro the action of the MI on human male gamete performance. Sperm samples were evaluated from 51 men: 21 healthy normozoospermic and 30 oligoasthenoteratozoospermic (OAT). In the latter group, 15 patients were orally treated with the nutraceutical mix and in the remaining 15 patients only MI was used directly on their ejaculated sperm. Comparing the pathologic samples with respect to normal samples we observed that motility, viability, Bcl-2 phosphorylation, and cholesterol efflux increased after in vitro and in vivo treatments. Glucose-6-phosphate dehydrogenase activity as well as triglycerides level and lipase activity highlighted an enhancement of energy expenditure upon the treatment. Uncapacitated sperm is characterized by an anabolic metabolism, to generate an energy reservoir which will be spent during the capacitation, an energy-consuming process needed to acquire the competence for the fertilization. Intriguingly, our finding highlights that the treatment with these substances facilitated the switch from uncapacitated to capacitated sperm, promoting the acquisition of the male gamete fertilizing capacity. Our data suggested that these substances act both directly on sperm and on spermatogenesis, improving the performance of OAT sperm invitro and invivo. The positive effects of these treatments could be of great help for men and couples who have difficulty to conceive achild in anatural way and/or during medical-assisted reproduction.Abbreviations: 30 OAT-untreated patients; B: 15 OAT patients treated in vivo; Bovine serum albumin (BSA); C: 15 OAT patients treated in vitro; cholesterol oxidase-peroxidase (CHOD-POD); H: Normozoospermic samples; HM: sperm from normospermic patients treated in vitro with MI; MI: Myoinositol: IM: Immobile motility; NP: Non-progressive motility; OAT: Oligoasthenoteratozoospermic; PPP: Pentose Phosphate Pathway; PR: Progressive motility; WHO: World Health Organization.

Clinical observation of herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS for asthenospermia and oligospermia / 中国针灸

OBJECTIVE@#To observe the clinical effect of herb-separated moxibustion on segmental conception vessel combined with low-frequency transcutaneous electrical acupoint stimulation (TEAS) for asthenospermia and oligospermia.@*METHODS@#A total of 105 patients with asthenospermia and oligospermia were randomly divided into a combination group, a TEAS group and a medication group, 35 cases in each one. In the medication group, vitamin E capsules, coenzyme Q10 capsules，@*RESULTS@#Compared before treatment, except for the sperm morphology 2 months into treatment in the medication group, the semen routine indexes 2, 3 months into treatment were improved in the 3 groups (@*CONCLUSION@#Herb-separated moxibustion on segmental conception vessel combined with low-frequency TEAS can improve semen routine, reduce sperm oxidative stress damage for patients with asthenospermia and oligospermia, and the clinical efficacy is better than the medication and TEAS.

[on oligozoospermia and asthenospermia].

OBJECTIVE: To observe the clinical effect of Yihechun Capsules (YHC) on oligozoospermia and asthenospermia. METHODS: A total of 181 male patients with infertility were randomly divided into a YHC+Levocarnitine (LC) group (n = 93, including 42 cases of oligozoospermia, 20 cases of asthenospermia and 31 cases of oligoasthenospermia) and an LC control group (n = 88, including 39 cases of oligozoospermia, 22 cases of asthenospermia and 27 cases of oligoasthenospermia), the former treated with YHC (ï¼»0.3 g per capsuleï¼½, once 4 capsules, bid, 30 minutes after meal) combined with LC oral liquid (2－3 g/d, tid, at mealtime) and the latter with LC oral liquid only (2－3 g/d, tid, at mealtime). After 3 months of treatment, comparisons were made between the two groups of patients in sperm concentration, the percentages of grade a and grade a+b sperm, and the rate of pregnancy. RESULTS: Of the 181 patients, 5 in the YHC+LC group and 2 in the LC control group failed to complete the course of treatment. There were no statistically significant differences between the two groups of patients in the baseline sperm concentration and the percentages of grade a and grade a+b sperm (P > 0.05), wich were all markedly increased in both the YHC+LC and the LC control groups (P < 0.05) after 3 months of treatment. And the patients of the YHC+LC group, compared with the controls, showed even more significant increases, as the oligozoospermia patients in sperm concentration (ï¼»21.07 ± 6.98ï¼½ vs ï¼»16.56 ± 1.82ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»27.53 ± 3.34ï¼½% vs ï¼»26.88 ± 1.35ï¼½%, P < 0.05) and grade a+b sperm (ï¼»53.32 ± 3.16ï¼½% vs ï¼»52.63 ± 2.48ï¼½%, P < 0.05), the asthenospermia patients in sperm concentration (ï¼»26.36 ± 3.37ï¼½ vs ï¼»24.42 ± 2.21ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»25.28 ± 4.64ï¼½% vs ï¼»21.32 ± 3.28ï¼½%, P < 0.05) and grade a+b sperm (ï¼»49.19 ± 2.87ï¼½% vs ï¼»45.64 ± 1.78ï¼½%, P < 0.05), and the oligoasthenospermia patients in sperm concentration (ï¼»19.38 ± 3.39ï¼½ vs ï¼»18.75 ± 1.35ï¼½ ×106/ml, P < 0.05) and the percentages of grade a sperm (ï¼»22.65 ± 4.81ï¼½% vs ï¼»21.31 ± 2.42ï¼½%, P < 0.05) and grade a+b sperm (ï¼»48.74 ± 5.61ï¼½% vs ï¼»44.36 ± 1.32ï¼½%, P < 0.05). The pregnancy rate was dramatically higher in the YHC+LC than in the LC control group (36.4% ï¼»32/88ï¼½ vs 15.1% ï¼»13/86ï¼½, P < 0.01). CONCLUSIONS: Yihechun Capsules combined with Levocarnitine oral liquid is evidently effective for the treatment of oligozoospermia and asthenospermia.

Compound Xuanju Capsule combined with western medicine for the treatment of male oligoasthenotspermia: A protocol for systematic review and meta-analysis.

BACKGROUND: Oligoasthenotspermia is a condition in which the number and motility of sperm in the semen of fertile men are lower than the normal level. Oligoasthenotspermia not only causes damage to the reproductive system, but also causes infertility in severe cases. Compound Xuanju capsule is a kind of Chinese patent medicine. Traditional medicine believes that compound Xuanju capsule can nourish kidney Yang, benefit kidney essence, improve semen quality, and treat infertility caused by oligoasthenotspermia. Clinical practice shows that compound Xuanju capsule combined with western medicine has a good therapeutic effect on male oligoasthenotspermia, but there is no evidence of evidence-based medicine. The purpose of this study is to systematically evaluate the efficacy and safety of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia, and to improve the evidence-based basis for the clinical application of compound Xuanju capsule in the treatment of male oligoasthenotspermia. METHODS: A systematic search was performed by retrieving on English database (PubMed, Embase, Web of Science, and The Cochrane Library) and Chinese database (CNKI, Wanfang, Weipu (VIP), CBM). Besides, manually search for Google and Baidu academic of compound XuanJu capsule combined western medicine in the treatment of male oligoasthenotspermia in randomized controlled clinical research. The retrieval time limit was from the establishment of the database to July 2020. Two researchers independently extracted and evaluated the quality of the data in the included study. A meta-analysis was performed using RevMan5.3 software, no language restrictions. RESULTS: In this study, the efficacy and safety of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia were evaluated by the total effective rate, semen parameters and other indexes. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number: DOI 10.17605/OSF.IO/2PM8T.