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1.
Phytomedicine ; 129: 155681, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38718638

RESUMEN

BACKGROUND: Infertility patients account for an astonishing proportion of individuals worldwide. Due to its complex etiology and challenging treatment, infertility has imposed significant psychological and economic burdens on many patients. C. Herba (Cistanche tubulosa (Schenk) Wight and Cistanche deserticola Ma), renowned as one of the most prominent Chinese herbal medicines (CHMs), is abundant in diverse bioactive compounds that exhibit therapeutic effects on many diseases related to oxidative stress (OS) and disorders of sex hormone levels. OBJECTIVE: Due to the limited drugs currently used in clinical practice to improve reproductive outcomes and their inevitable side effects, developing safe and effective new medications for infertility is of significance. This article comprehensively reviewed the phytochemicals of C. Herba, focusing on their efficacy and mechanisms on infertility and their safety for the first time, aiming to offer valuable insights for the development and application of C. Herba, and for developing novel strategies for treating infertility. METHODS: We used "Cistanche" and its known bioactive components in combination with "sperm", "testicles", "epididymis", "ovaries", "uterus", and "infertility" as keywords to search in PubMed, Web of Science, Scopus and CNKI up to November 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: The therapeutic effects of C. Herba on infertility are mainly attributed to echinacoside (ECH), verbascoside (VB), salidroside (SAL), polysaccharides, and betaine. They can effectively improve spermatogenic dysfunction, gonadal dysfunction and erectile dysfunction (ED) by exerting anti-oxidation, sex hormones regulation and anti-hypoxia. Moreover, they can also improve premature ovarian failure (POF), ovarian and uterine cancer, oocyte maturation by exerting anti-oxidation, anti-apoptosis, and anti-cancer. C. Herba and its active ingredients also exhibit pleasing safety. CONCLUSION: C. Herba is a promising source of natural medicine for infertility. Additionally, compared to current therapeutic drugs, its favorable safety also supports its development as a nutritional supplement. However, high-quality clinical studies are required to validate its effectiveness for the development of novel therapeutic strategies.


Asunto(s)
Cistanche , Medicamentos Herbarios Chinos , Animales , Femenino , Humanos , Masculino , Cistanche/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/química , Glucósidos/farmacología , Glucósidos/uso terapéutico , Glicósidos , Infertilidad/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Fenoles/farmacología , Fenoles/uso terapéutico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Polifenoles , Reproducción/efectos de los fármacos
2.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1594-1601, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621944

RESUMEN

The ovarian germline stem cells(OGSCs) cultured in the optimized culture system were used as the research object to observe the effect of Tripterygium glycosides(TG) on OGSCs and explore the mechanism of reproductive toxicity by the Notch signaling pathway. Cell counting kit-8(CCK-8) was used to observe the viability level of OGSCs in mice cultured in vitro by TG of 3.75, 7.5, and 15 µg·mL~(-1). Immunofluorescence technology and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the protein and gene expression level of OGSCs marker mouse vasa homologue(MVH) and octamer-binding transcription factor 4(Oct4) by TG of 3.75 µg·mL~(-1). RT-PCR detected the gene expression of neurogenic locus Notch homolog protein 1(Notch1), Hes family BHLH transcription factor 1(Hes1), and jagged canonical Notch ligand 1(Jagged1). The RNA was extracted for transcriptome analysis to analyze the mechanism of action of TG intervention on OGSCs. 3.75 µg·mL~(-1) of TG was combined with 40 ng·mL~(-1) Notch signaling pathway γ-secretagocin agonist jagged canonical notch ligand(Jagged) for administration. CCK-8 was used to detect the viability level of OGSCs. Double immunofluorescence technology was used to detect the protein co-expression of MVH with Hes1, Notch1, and Jagged1. The results showed that compared with the blank group, the TG administration group significantly inhibited the activity of OGSCs(P<0.01 or P<0.001). It could reduce the protein and gene expression of OGSC markers, namely MVH and Oct4(P<0.05, P<0.01, or P<0.001). It could significantly inhibit the gene expression of Notch1, Hes1, and Jagged1(P<0.001). Transcriptomic analysis showed that TG affected the growth and proliferation of OGSCs by intervening Jagged1, a ligand associated with the Notch signaling pathway. The experimental results showed that the combination of Notch signaling pathway γ-secretagorein agonist Jagged could significantly alleviate the decrease in OGSC viability induced by TG(P<0.001) and significantly increased the OGSC viability compared with the TG group(P<0.001). It also could significantly increase the co-expression of MVH/Jagged1, MVH/Hes1, and MVH/Notch1 proteins(P<0.01 or P<0.001). It suggested that TG play the role of γ-secretagorease inhibitors by downregulating the OGSC markers including MVH and Oct4 and Notch signaling pathway molecules such as Notch1, Hes1, and Jagged1, participate in the OGSC pathway, and mediate reproductive toxicity caused by the Notch signaling pathway.


Asunto(s)
Células Madre Oogoniales , Ratones , Animales , Células Madre Oogoniales/metabolismo , Tripterygium , Ligandos , Transducción de Señal
3.
J Pharm Biomed Anal ; 245: 116166, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38669816

RESUMEN

The study aimed to investigate the relieving effect of QingYan Formula (QYF) in treating perimenopausal syndrome. A combination of metabonomic analysis and in vitro pharmacodynamic experiments was employed to achieve this objective.Over a period of 12 weeks, ovariectomized (OVX) rats were orally administered QYF's 70 % ethanol extract or estradiol valerate (EV). The results demonstrate that QYF restored the estrous cycle of ovariectomized rats and exhibited significant estrogenic activity, as indicated by reversal of uterine and vagina atrophy, improvement of serum estradiol level and decrease of serum luteinizing hormone(LH) level. Additionally, QYF administration effectively reduced high bone turnover and repaired trabecular microstructure damage. Metabonomic analysis of the OVX rats treated with QYF revealed the identification of 55 different metabolites in the serum, out of which 35 may be potential biomarkers. QYF could regulate the disturbed metabolic pathways including the Biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, bile secretion, and steroid hormone biosynthesis. PI3KCA, SRC, and MAPK3 are potential therapeutic targets for QYF therapeutic effects. These findings support the efficacy of QYF in alleviating perimenopausal syndrome and regulating lipid metabolic disorders in OVX rats.


Asunto(s)
Medicamentos Herbarios Chinos , Metabolómica , Ovariectomía , Perimenopausia , Ratas Sprague-Dawley , Animales , Femenino , Metabolómica/métodos , Medicamentos Herbarios Chinos/farmacología , Ratas , Perimenopausia/efectos de los fármacos , Estradiol/sangre , Estradiol/farmacología , Cromatografía Líquida de Alta Presión/métodos , Biomarcadores/sangre , Hormona Luteinizante/sangre , Ciclo Estral/efectos de los fármacos , Útero/efectos de los fármacos , Útero/metabolismo , Modelos Animales de Enfermedad
5.
J Ethnopharmacol ; 322: 117570, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38110131

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola (C. deserticola) is an edible and traditional medicine widely used in China, which has been confirmed to be effective in the treatment of postmenopausal osteoporosis (PMOP). Despite its proven efficacy, the exact role of C. deserticola in bone metabolism and its underlying mechanism has remained unclear. AIM OF THE STUDY: In this research, we employed an in vivo model utilizing ovariectomized (OVX) rats to characterize the anti-osteoporotic activity and metabolic mechanism of the ethanol extract of C. deserticola (CHE). MATERIALS AND METHODS: Fifty female Sprague-Dawley (SD) rats were randomly divided into five groups including sham operation group, model group, 0.1 g/kg estradiol valerate (EV) group as the positive control, low (0.6 g/kg) and high (1.2 g/kg) dosage CHE groups. Biochemical parameter analyses and histopathological experiments were conducted to assess the pharmacodynamic effects. Metabolomic analysis was conducted on serum samples to examine the metabolic profiles, identify potential biomarkers, and elucidate the metabolic pathways associated with CHE in OVX rats. RESULTS: CHE treatment demonstrated significant anti-osteoporosis activity by regulating serum biochemical markers of bone turnover, improving cancellous bone structure, and reversing the decrease in bone mineral density. Furthermore, the clinical equivalent dose group (CHL) achieved superior overall outcomes. The main interventions of CHE on OVX rats involved the modulation of several key pathways, including steroid hormone biosynthesis, arachidonic acid metabolism, tyrosine and tryptophan metabolism, biotin metabolism, regulation of TRP channels by inflammatory mediators, primary bile acid biosynthesis, regulation of lipolysis in adipocytes, and bile secretion. 23 potential efficacy-related biomarkers within the metabolic network were identified. Among them, long-chain unsaturated fatty acids (eg. DHA and docosapentaenoic acid), steroid hormones, amino acids and carbohydrates were strongly correlated with bone resorption and formation markers. Additionally, it was observed four pathways (nucleotide, carbon, amino acid, and lipid metabolism) were implicated in the effects of CHE. CONCLUSION: This study demonstrates that CHE improves bone loss in PMOP mainly through regulating lipid metabolism pathways, which provides an evidence base for CHE treatment of PMOP.


Asunto(s)
Cistanche , Osteoporosis Posmenopáusica , Osteoporosis , Humanos , Ratas , Femenino , Animales , Ratas Sprague-Dawley , Cistanche/química , Cromatografía Líquida de Alta Presión , Metabolismo de los Lípidos , Osteoporosis/metabolismo , Osteoporosis Posmenopáusica/tratamiento farmacológico , Estradiol/uso terapéutico , Metabolómica , Aminoácidos/metabolismo , Biomarcadores/metabolismo , Ovariectomía
6.
Phytomedicine ; 105: 154360, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35964457

RESUMEN

BACKGROUND: Panlongqi Tablet (PLQT) is a Chinese patent drug composed of 29 kinds of traditional Chinese medicines. Clinical practice has shown that PLQT can relieve osteoarthritis-caused joint pain, but its effects and mechanisms in other pathological links of osteoarthritis have not been characterized. PURPOSE: The purpose of this study is to reposition the pharmacodynamic effects of PLQT through network pharmacology analysis combined with experimental validation, and also to preliminarily explore its possible mechanism. METHODS: On the basis of integrating the relevant targets of PLQT in multiple drug databases and osteoarthritis-related targets in the disease database, an interaction network of related genes was constructed. The hub candidate targets of PLQT in the treatment of osteoarthritis were determined by calculating the main network topological characteristics, The specific functions and pathways of these targets acting on osteoarthritis were modularly analyzed. In addition, the modified Hulth-induced rat model of osteoarthritis and IL-1ß-induced in vitro model of osteoarthritis were established to further validate the potential efficacy and possible mechanism of PLQT. RESULTS: A total of 138 key targets related to osteoarthritis were selected based on topological parameters, and their biological functions were mainly enriched in four over-expressed modules of cartilage degeneration, inflammatory response, immune response, and subchondral bone metabolism. The hub candidate targets had the highest enrichment degree in the TLR4-RAC1-PIK3CA-Akt-NFκB signaling axis of the PI3K/Akt signaling pathway. In vivo results showed that PLQT treatment significantly inhibited the degeneration of proteoglycan and collagen in the cartilage of osteoarthritis rats, suppressed chondrocyte apoptosis, and reduced the Mankin score of joints. Moreover, PLQT alleviated synovial inflammation, reduced the Krenn score of synovium, inhibited the formation of osteophytes in osteoarthritis rats, reduced the bone mineral density (BMD), fractional bone volume (BV/TV), and trabecular thickness (Tb.Th.), as well as increased the trabecular separation (Tb.Sp.) of subchondral bone and the thickness of the subchondral bone plate (SBP.Th.). PLQT suppressed the expressions of TLR4, RAC1, PIK3CA, p-Akt, MMP-13, and ADAMTS-5 in the cartilage, and inhibited the expression of NFκB p65 in the chondrogenic nucleus. Meanwhile, as downstream effector factors of the predictive pathways, the levels of serum interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) were decreased after PLQT treatment. In vitro results also showed that PLQT could inhibit the expression of key proteins and downstream effector factors of the signaling axis, and this inhibition disappeared when pathway agonists were added. CONCLUSION: PLQT exerted pharmacological effects on the key pathological links of osteoarthritis including chondrocyte apoptosis, extracellular matrix degradation, inflammation, and subchondral bone metabolism by inhibiting the TLR4-RAC1-PIK3CA-Akt-NFκB axis-related proteins.


Asunto(s)
Osteoartritis , Receptor Toll-Like 4 , Animales , Fosfatidilinositol 3-Quinasa Clase I , Medicamentos Herbarios Chinos , Inflamación , FN-kappa B , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas
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