Scientific Reports
·
2019
·Vol. 9
·期 1
·1-5
·
IF 4.011
Mei Jianfeng,Chen Xiang,Liu Jianghua,Yi Yu,Zhang Yanlu,Ying Guoqing
Genistein is known to have multiple biological activities and has great potential for use as a preventative medicine and in disease treatment. Genistein can be extracted from plants, but also can be obtained from its glycoside form, sophoricoside, which is more abundant in some plants. Biotransformation by unpurified microbial enzymes has the advantage of low cost and is a preferred method for production of natural compounds. This study isolated a strain of Rhizopus oryzae that could produce β -glucosidase, which efficiently hydrolyzes sophoricoside into genistein, from an enrichment culture of the dried fruits of Sophora japonica . After the composition of enzyme-producing medium and biotransformation conditions were optimized, a genistein yield of 85.6% was obtained after 24 h in a shake-flask biotransformation at pH 7.0 using an initial substrate concentration of 1 g/L. The developed process provides an alternative method for production of genistein, and would be suitable for scale-up production in the pharmaceutical industry.
研究领域:
微生物学
·
药理学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Hefei Wang,Dewei He,Zhe Li,Xiyu Gao,Shuo Yang,Mingchi Cui,Bojian Ye,Bingxu Huang,Shoupeng Fu,Dianfeng Liu
Neuronal apoptosis and neuroinflammation are key factors involved in the pathological changes of Parkinson's disease (PD). Sophoricoside (SOP) has shown anti-inflammatory and anti-apoptosis effects in various diseases. However, the role of SOP in PD has not been reported. In this experiment, we found that oral administration of SOP alleviated weight loss and motor symptoms in 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-injected mice. Further studies revealed that SOP inhibited inflammatory responses and neuronal apoptosis in the midbrain region of MPTP-injected mice. In vitro mechanistic study, we found that SOP exerts neuroprotective effects through a two-sided action. On the one hand, SOP inhibits Lipopolysaccharide (LPS)-induced inflammatory responses in microglia by inhibiting the Nuclear factor kappa-B(NF-κB) pathway. On the other hand, SOP inhibits 1-methyl-4-phenylpyridinium (MPP + )-induced neuronal apoptosis by regulating the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Thus SOP is expected to be a potential therapeutic agent for PD by targeting neuroinflammation and neuronal apoptosis.
研究领域:
神经科学
·
药理学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Catalysis
·
2022
·
IF 5.089
Ruizhi Han,Baocheng Chai,Yulin Jiang,Jie Ni,Ye Ni
Poor water solubility limits the application of genistein in food and pharmaceutical fields. Glycosylation can greatly improve the water solubility of genistein by attaching long chain sugars. Here, glycosylation of sophoricoside (genistein monoglucoside) by cyclodextrin glycosyltransferase from Paenibacillus macerans ( Pm CGTase) was investigated. Based on molecular docking and hydrolytic activity analysis, saturation mutagenesis was conducted at residues Y195 and S77 of Pm CGTase. Variants S77N, Y195S, Y195I, S77N/Y195S, and S77N/Y195I showed enhanced product specificity toward long-chain glycosylated sophoricosides (LCGS). In particular, S77N/Y195I displayed 119% increased LCGS product specificity and 20.6% higher sophoricoside conversion than the wild type. Increased comprehensive activities of Y195S and Y195I contributed to enhanced conversion, and decreased hydrolytic activity of S77N promoted LCGS accumulation. Kinetics results revealed improved catalytic efficiency and substrate affinity of variants toward both the glycosyl donor and acceptor. Furthermore, MD simulation elucidates that the decreased substrate binding energy of variants could lead to improved kinetics, and increased hydrogen binding between residues at -6/-7 subsites and the glycosyl donor is primarily responsible for enhanced LCGS specificity. An “Increased Income-Reduced Expenditure” mechanism was proposed, explaining that the enhanced LCGS product specificity of Pm CGTase is closely related to the increased hydrogen bond interactions at -6/-7 subsites and decreased hydrolytic activity.
研究领域:
生物化学
·
酶工程
·
药学
·
食品科学
✓ 已验证
产品关联
DOI
高影响因子
Biochemistry and Biophysics Reports
·
2024
·
IF 2.3
Youyang Liu,Yunlu Zhao,Qi Guo,Pengfei Wang,Peixuan Li,Qingqing Du,Huazhou Xu,Qingyin Yu,Xiaoyi Zhao,Weiya Zhang,Shengjun An,Shuhui Wu
Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from Sophora japonica . We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing in vitro experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.
研究领域:
免疫学
·
药理学
·
风湿病学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Jiaao Shen,Zijia Man,Weiwei Li,Mengqi Guo,Zefeng Xiang,Long Ma,Xianjiang Kang,Shuai Guo
Background The incidence and mortality rates of lung cancer have consistently ranked highest among all cancers for an extended period. Identifying specific targets and developing effective drugs is crucial. In this study, we discovered that the natural compound sophoricoside, derived from Sophora japonica, targets the TMEM16A ion channel for lung cancer treatment. Methods Whole-cell patch clamp experiments were conducted to evaluate the inhibitory efficacy of sophoricoside on TMEM16A. Molecular dynamics simulations were performed to predict the affinity and the gating-related conformational changes of sophoricoside within TMEM16A. Cell proliferation, migration, and apoptosis experiments were employed to detect the regulation of sophoricoside on lung cancer cell growth. Western blot analyses were carried out to investigate the signaling mechanisms underlying the regulation of lung cancer growth by sophoricoside. In vivo xenograft tumor models were utilized to evaluate the anticancer efficacy and biosafety profile of sophoricoside. Results Sophoricoside inhibited the TMEM16A whole-cell current in a concentration-dependent manner, with an IC 50 of 14.8 ± 1.2 μM. Molecular dynamics simulations confirmed that sophoricoside bond to the extracellular vestibular region of TMEM16A, blocking chloride ion transport by inducing constriction of the hydrophobic pore regions. Subsequently, we investigated the regulatory effects of varying concentrations of sophoricoside on the growth of LA795 cells. Knocking down TMEM16A in LA795 cells and overexpressing TMEM16A in 16HBE cells established that TMEM16A was a critical target of sophoricoside. Western blot experiments demonstrated that sophoricoside inhibited the growth of LA795 cells via the several signal transduction pathways. In vivo results revealed that sophoricoside exhibits both potent anticancer effects and satisfactory biosafety. Conclusion This study identifies the natural product sophoricoside as a potential agent targeting TMEM16A to inhibit lung cancer growth, presenting a promising candidate for lung cancer treatment drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Shaowei Zheng,Ya Gao,Houkang Cao,Kai Guo,Wenxiu Wang,Guiying Lu,Shasha Wang,Mingli Zhong,Bo Li,Kefeng Zhang,Riming Wei,Jianzhao Wu
Background Acute liver failure (ALF) is associated with ferroptosis and currently lacks specific drugs and therapies. Previous studies have shown the hepatoprotective activity of Sophoricoside (SOP) in diverse models of hepatic injury. However, the role of SOP in ALF caused by lipopolysaccharide (LPS)/D-galactosamine (D-GalN) is still unknown. Purpose To investigate the therapeutic effects of SOP on ALF and its underlying mechanisms of action. Methods In vivo , an ALF mouse model was established using LPS and D-GalN. RNA sequencing was used to identify differentially expressed genes, which were subsequently confirmed by Western blot and qRT-PCR. In vitro , erastin was used to induce ferroptosis in HepG2 cells. Subsequently, the cells were treated with SOP, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385, and the glutathione peroxidase 4 (GPX4) inhibitor RSL3. Additionally, siRNA was utilized for Nrf2 knockdown. Measurements of biochemical markers, reactive oxygen species (ROS) levels, alterations in mitochondrial membrane potential, qRT-PCR, and Western blot analysis were used to confirm the effectiveness and mechanism of SOP. Finally, the interaction between SOP and Nrf2 was verified through molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA). Results In vivo , experimental analysis revealed that SOP ameliorated liver injury, hepatocyte Fe 2+ accumulation, and oxidative stress. RNA sequencing analysis indicated that SOP reversed the abnormal expression of genes related to Nrf2 and the ferroptosis pathway. In vitro , SOP ameliorated erastin-induced oxidative stress, ROS accumulation, and mitochondrial membrane potential loss. After the application of pharmacological inhibitors and siRNA knockdown, the SOP’s inhibitory effect on ferroptosis was antagonized. Conclusion SOP alleviated ALF by activating the Nrf2/GPX4 signaling pathway, thereby mitigating oxidative stress and ferroptosis.
研究领域:
药理学
·
分子生物学
·
肝病学
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
·
2025
·
IF 1.9
Shuang Jin,Yubin Ren,Hongyao Cai,Biqiong Chen,Yupeng Cheng,Weili Liu,Cailiang Peng,Yujie Fu,Chen Lv,Huiling Li
This study introduces a green, sustainable, and efficient approach for biotransforming sophoricoside into genistein from Fructus Sophorae using Aspergillus oryzae by removal of one molecule of glucose by β-glucosidase, an edible microorganism immobilized on magnetic cellulose and treated with deep eutectic solvents (DES). The goal was to enhance the biotransformation ratio by optimizing reaction conditions and selecting the most suitable DES. Various DESs, including natural deep eutectic solvents (NADES), were assessed for their ability to improve catalytic performance. Among them, the NADES system comprising choline chloride (CHCL) and glycerol (G) exhibited the highest catalytic efficiency (32.19 mg/g) under optimal conditions: temperature 33 °C, time 65 hours, pH 5.5, and a liquid-to-solid ratio of 45:1 (mL/g). This yield was 10.60 times greater than the genistein yield from untreated F. Sophorae. This combination notably increased cell membrane permeability, aiding the bioconversion process. The cellulose immobilization technique provided a stable and reusable microreactor and maintained microbial activity (80.37%) over 10 cycles. These findings validate the bioconversion method as a promising and sustainable strategy for genistein production from plant-derived sophoricoside, with potential applications in pharmaceutical and nutraceutical industries.
研究领域:
生物化学
·
制药工程
·
可持续化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）