Community ecological succession of endophytic fungi associates with medicinal compound accumulation in Sophora alopecuroides.

Endophytic fungi of medicinal plants are symbiotic with the host and play an important role in determining metabolites. To understand the relationship between the accumulation of Sophora alopecuroides' medicinal bioactive compounds and the ecological succession of endophytic fungi, here we collected samples from S. alopecuroides at four developmental stages (adult, flowering, podding, and mature) and different organs (roots, stems, leaves, and seeds) at the mature stage. We then used high-performance liquid chromatography-mass spectrometry and high-throughput sequencing on the internal transcribed spacer region to identify the medicinal compounds and endophytic fungal communities in each sample. The endophytic fungal community characteristics and accumulation of medicinally bioactive compounds of S. alopecuroides varied with the host's developmental stages and organs, with the highest total alkaloids content of 111.9 mg/g at the mature stage. Membership analysis and network connection analysis showed a total of 15 core endophytic fungi in different developmental stages and 16 core endophytic fungi in different organs at the mature stage. The unclassified Ascomycota, Aspergillus, and Alternaria were significantly and positively correlated with the medicinal compounds of S. alopecuroides at the mature stage (r > 0.6 or r < -0.6; P < 0.05). In this study, we identified key endophytic fungal resources that affect the content of medicinally bioactive compounds in S. alopecuroides. This discovery could lay the foundation for enhancing the yield of medicinally bioactive compounds in S. alopecuroides and the development and application of functional endophytic fungi.IMPORTANCESophora alopecuroides is a traditional Chinese herbal medicine. The major medicinal chemicals are considered to be quinolizidine alkaloids. Quinolizidine alkaloids have been widely used for the treatment of tumors, dysentery, and enteritis. Previous studies have found that endophytic fungi in S. alopecuroides can promote the accumulation of host quinolizidine alkaloids. However, the relationship between the accumulation of S. alopecuroides' medicinal bioactive compounds and the ecological succession of endophytic fungi remains unclear. In this study, we screened the key endophytic fungal resources affecting the content of medicinally bioactive compounds and laid the foundation for subsequent research on the mechanism by which endophytic fungi promote the accumulation of medicinally bioactive compounds in S. alopecuroides.

The total alkaloids of Sophora alopecuroides L. improve depression-like behavior in mice via BDNF-mediated AKT/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression has become a global public health problem and the development of new highly effective, low-toxicity antidepressants is imminent. Sophora alopecuroides L. is a common medicinal plant, which has therapeutic effect on central nervous system diseases. AIM OF THE STUDY: In this study, the antidepressant effect of total alkaloids (ALK) isolated from Sophora alopecuroides L. was explored and the mechanism was further elucidated. MATERIALS AND METHODS: A primary neuronal injury model was established in vitro by corticosterone. ICR mice were then selected to construct an in vivo model of chronic unpredictable mild stress (CUMS)-induced depression, and the ameliorative effects of ALK on depression were examined by various behavioral tests. The antidepressant molecular mechanism of ALK was subsequently revealed by ELISA, Western blot, immunohistochemistry and Golgi staining. RESULTS: BDNF secretion as well as TrkB and ERK phosphorylated protein levels were found to be improved in primary cortical neurons, along with improved dendritic complexity of neurons. The results of in vivo showed that the depression-like behavior of CUMS-induced mice was reversed after 2 weeks of continuous gavage administration of ALK, and the neurotransmitter levels in the plasma of mice were increased. Moreover, the expression levels of key proteins of BDNF-AKT-mTOR pathway and the complexity of neuronal dendrites were improved in the prefrontal cortex of mice. CONCLUSIONS: These findings indicate that ALK of Sophora alopecuroides L. can effectively improve the depressive phenotype of mice, possibly by promoting the expression of BDNF in prefrontal cortex, activating the downstream AKT/mTOR signal pathway, and ultimately enhancing neuronal dendritic complexity.

A randomized controlled trial on the seeds of Sophora alopecuroides var. alopecuroides for the treatment of acute heroin withdrawal syndrome.

BACKGROUND: and purpose: The seeds of Sophora alopecuroides var. alopecuroides have attenuated the acute opium withdrawal syndrome in humans. Therefore, the efficacy and safety of a standardized extract of the plant for the treatment of acute heroin withdrawal syndrome was evaluated in abstinent heroin addicts. MATERIALS AND METHODS: The patients were randomized to take three 400 mg extract capsules (N = 50) or placebo (N = 50) once per day orally for eight days. The severity of withdrawal syndrome was assessed by the clinical opiate withdrawal scale (COWS) as the primary outcome measure at the baseline and on the days 3 and 8. The hepatic and renal functions and complete blood count were the secondary outcome measures tested at the baseline and end of the study. RESULTS: The COWS score decreased in both groups after eight days, but the decrease was significantly higher in the experimental group (p < 0.001); the effect size of the decrease was 2.64. The groups had significant differences in the COWS scores on the days 3 and 8 (p < 0.001 for both). The extract had no significant effect on the other parameters. No side effect was noted. CONCLUSION: The extract seems to alleviate acute heroin withdrawal syndrome safely.

Sophora alopecuroides Alleviates Neuroinflammation and Oxidative Damage of Parkinson's Disease In Vitro and In Vivo.

For centuries, Sophora alopecuroides L. has been used both as a food and an herbal medicine in northern China. A new cytisine-type alkaloid, N-methylene-(5,7,4[Formula: see text]-trihydroxy)-isoflavone (LY01), was found in the fruits of Sophora alopecuroides L. and shows neuroprotective effects against Parkinson's disease (PD). PD is a frequently occurring, irreversible neurodegenerative disease that seriously threatens the health of the elderly population. There is no cure for PD. The available treatments help manage the symptoms, but their use is limited by multiple side effects. Therefore, more pharmacological treatments addressing this pathology are urgently required. This study aimed to evaluate the neuroprotective effects of LY01 against PD, as well as their underlying mechanisms, using both in vitro and in vivo experimental models. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-induced mouse model of PD was used to assess the effects of LY01 on the motor coordination deficit, progression of the pathology, and molecular characteristics. 1-Methyl-4-phenylpyridinium (MPP[Formula: see text])-activated SH-SY5Y cells and lipopolysaccharide (LPS)-activated BV-2 cells were used to evaluate LY01 effects on oxidative damage and neuroinflammation. In the rotarod test, LY01 alleviated the impaired motor coordination in PD mice. Furthermore, LY01 treatment prevented the loss of dopaminergic neurons in the substantia nigra and striatum of the PD mice, reduced neuroinflammation in the mice with MPTP-induced PD and the LPS-activated BV-2 cells, and diminished oxidative stress in the PD mice and the MPP[Formula: see text]-induced SH-SY5Y cells. In conclusion, these results suggest the potential of LY01 as a therapeutic agent for treating PD.

Synergistic anticancer effect of flavonoids from Sophora alopecuroides with Sorafenib against hepatocellular carcinoma.

Sorafenib (SF), a multi-kinase inhibitor, is the first FDA-approved systemic chemotherapy drug for advanced hepatocellular carcinoma (HCC). However, its clinical application is limited by severe toxicity and side effects associated with high applied doses. Sophora alopecuroides L. is traditionally used as Chinese herbal medicine for treating gastrointestinal diseases, bacillary dysentery, viral hepatitis, and other diseases, and exerts an important role in anti-tumor. Hence, we investigated the synergistic actions of seventeen flavonoids from this herb combined with SF against HCC cell lines and their primary mechanism. In the experiment, most compounds were found to prominently enhance the inhibitory effects of SF on HCC cells than their alone treatment. Among them, three compounds leachianone A (1), sophoraflavanone G (3), and trifolirhizin (17) exhibited significantly synergistic anticancer activities against MHCC97H cells at low concentration with IC50 of SF reduced by 5.8-fold, 3.6-fold, and 3.5-fold corresponding their CI values of 0.49, 0.66, and 0.46 respectively. Importantly, compounds 3 or 17 combined with SF could synergistically induce MHCC97H cells apoptosis via the endogenously mitochondrial-mediated apoptotic pathway, involving higher Bax/Bcl-2 expressions with the activation of caspase-9 and -3, and arrest the cell cycle in G1 phases. Strikingly, this synergistic effect was also closely related to the co-suppression of ERK and AKT signaling pathways. Furthermore, compound 3 significantly enhanced the suppression of SF on tumor growth in the HepG2 xenograft model, with a 79.3% inhibition ratio at high concentration, without systemic toxicity, compared to either agent alone. These results demonstrate that the combination treatment of flavonoid 3 and SF at low doses exert synergistic anticancer effects on HCC cells in vitro and in vivo.

Correlation in endophytic fungi community diversity and bioactive compounds of Sophora alopecuroides.

Sophora alopecuroides L. is a traditional Chinese medicine used for the treatment of several different disease states including bacillary dysentery and enteritis. But importantly, it also plays a role as an anti-tumor agent. That said, little is known about the role endophytes play regarding the clinically bioactive metabolites in S. alopecuroides. In order to explore the effects of endophytic fungi on the accumulation, quality, and correlation in the content of the medicinal compounds, the structural diversity of endophytic fungi in S. alopecuroides was analyzed. The relationship between endophytes and quinolizidine alkaloids (QAs), housed within the seeds of S. alopecuroides, which were interpreted based on established methods of high-throughput sequencing and high-performance liquid chromatography. A total of 1,034,418 effective sequence reads and 257 operational taxonomic units (OTUs) were obtained from 33 samples which were sourced from 11 different sampling sites and further classified into 9 phyla, 20 classes, 45 orders, 85 families, and 118 genera. Ascomycota was found to be the dominant phylum of endophytic fungi in S. alopecuroides, with a relative abundance ranging from 60.85 to 98.30%. Alternaria, Cladosporium, Filobasidium, and an unidentified Ascomycota were the core-shared endophytes, accounting for 49.96, 27.12, 14.83, and 7.88%, respectively. Correlation analysis showed that the Simpson's diversity index of endophytic fungal community in S. alopecuroides was significantly positively correlated with the Oxymatrine (OMA) content in different areas, while the Chao and Shannoneven indexes were significantly negatively correlated with OMA. The endophytic fungi of Alternaria were positively correlated with the content of OMA, Oxysophocarpine (OSC), and total QAs. This study has mastered the endophytic fungi resources of S. alopecuroides, explored potential functional endophytic fungi, and provided a scientific basis for using biological fertilization strategies to improve the quality of S. alopecuroides.

Research progresses on the main active components in Ningxia Sophora alopecuroides and the therapeutic activities for liver diseases / 药学实践杂志

Sophora alopecuroides, a plant of the family Leguminosae, is one of the Daodi herbs in Ningxia. The active constituents of Sophora alopecuroides are abundant and complex, including alkaloids, flavonoids, volatile oils, steroids, polysaccharides, fatty acids and so on. In recent decades, a great number of domestic and overseas studies have been carried out on Sophora alopecuroides alkaloids, which have anti-hepatitis, anti-liver fibrosis, anti-cirrhosis, anti-liver failure and anti-liver cancer and other pharmacological effects. Clinically, Matrine-related drugs are used to treat hepatitis B virus infection and other diseases. This review aims to summarize the main active ingredients of Sophora alopecuroides, mainly focusing on the research progress in their treatment activities for liver diseases.

TMT based proteomic profiling of Sophora alopecuroides leaves reveal flavonoid biosynthesis processes in response to salt stress.

Salt stress is the major abiotic stress worldwide, adversely affecting crop yield and quality. Utilizing salt tolerance genes for the genetic breeding of crops is one of the most effective measures to withstand salinization. Sophora alopecuroides is a well-known saline-alkaline and drought-tolerant medicinal plant. Understanding the underlying molecular mechanism for Sophora alopecuroides salt tolerance is crucial to identifying the salt-tolerant genes. In this study, we performed tandem mass tag (TMT) based proteomic profiling of S. alopecuroides leaves under 150 mM NaCl induced salt stress condition for 3 d and 7 d. Data are available on ProteomeXchange (PXD027627). Furthermore, the proteomic findings were validated through parallel reaction monitoring (PRM). We observed that the expression levels of several transporter proteins related to the secondary messenger signaling pathway were altered under salt stress conditions induced for 3 d. However, the expression of the certain transferase, oxidoreductase, dehydrogenase, which are involved in the biosynthesis of flavonoids, alkaloids, phenylpropanoids, and amino acid metabolism, were mainly alerted after 7 d post-salt-stress induction. Several potential genes that might be involved in salt stress conditions were identified; however, it demands further investigation. Although salt stress affects the level of secondary metabolites, their correlation needs to be investigated further. SIGNIFICANCE: Salinization is the most severe abiotic adversity, which has had a significant negative effect on world food security over the time. Excavating salt-tolerant genes from halophytes or medicinal plants is one of the important measures to cope with salt stress. S. alopecuroides is a well-known medicinal plant with anti-tumor, anti-inflammatory, and antibacterial effects, anti-saline properties, and resistance to drought stress. Currently, only a few studies have explored the S. alopecuroides' gene function, and regulation and these studies are mostly related to the unpublished genome sequence information of S. alopecuroides. Recently, transcriptomics and metabolomics studies have been carried on the abiotic stress in S. alopecuroides roots. Multiple studies have shown that altered gene expression at the transcript level and altered metabolite levels do not correspond to the altered protein levels. In this study, TMT and PRM based proteomic analyses of S. alopecuroides leaves under salt stress condition induced using 150 mM NaCl for 3 d and 7 d was performed. These analyses elucidated the activation of different mechanisms in response to salt stress. A total of 434 differentially abundant proteins (DAPs) in salt stress conditions were identified and analyzed. For the first time, this study utilized proteomics technology to dig out plentiful underlying salt-tolerant genes from the medicinal plant, S. alopecuroides. We believe that this study will be of great significance to crop genetics and breeding.

Matrine-Type Alkaloids from the Seeds of Sophora alopecuroides and Their Potential Anti-inflammatory Activities.

Three new matrine-type alkaloids, 8ß-hydroxyoxysophoridine (1), 9ß-hydroxysophoridine (2), 9ß-hydroxyisosophocarpine (3), together with one known analog, 11,12-dehydromatrine (4), were isolated from the seeds of Sophora alopecuroides L. The structures of new compounds were elucidated using extensive spectroscopic techniques including the experimental and calculated ECD data. The anti-inflammatory activities of all the isolates on NO production in RAW 264.7 cells stimulated by lipopolysaccharide were evaluated. Among them, 8ß-hydroxyoxysophoridine (1) showed a significant inhibitory effect with an IC50 value of 18.26 µM.

Evaluation of the wound healing potential of Sophora alopecuroides in SD rat's skin.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides Linn. (Leguminosae) has been largely used in traditional folk medicine in China as an anti-inflammatory agent and to treat various skin wounds, including sore furunculosis and ulcer (a common type of non-healing wound). The present study aimed to evaluate the effects of S. alopecuroides gel on skin wound healing in rats. MATERIALS AND METHODS: When the rats were anesthetized, full-thickness skin wound was performed on dorsal area by using biopsy punch with 8 mm diameter. Then, wounds received treatment with different doses of S. alopecuroides gel (1.25%, 2.5% and 5%, w/w) once a day with the gel base used as vehicle control and rb-FGF as positive control. Every five animals were sacrificed after 7, 12 days after surgery for histopathology and relevant biochemical indexes analysis. Besides, after RAW 264.7 cells exposure to LPS (1 µg/ml) with or without total extract (25 and 50 µg/ml) for 24 h, the culture supernatant was used for detection of IL-1ß and TNF-α levels using ELISA kits and the protein lysate for western blot analysis. RESULTS: A remarkable wound closure was observed after administration with 5% S. alopecuroides gel with the wound area of 30% and 8.5% as compared to 42% and 19% in the control group on day 7 and 12, respectively. Histological and immunostaining analysis for the wound tissues also revealed that S. alopecuroides promoted the growth of granulation tissue, collagen deposition, cell proliferation and angiogenesis. Meanwhile, it was able to ameliorate inflammatory response and promote the production of TGF-ß. In addition, we also demonstrated that S. alopecuroides inhibited the release of inflammatory mediators and expression of iNOS as well as up-regulated the expression of Arg-1 in LPS-triggered RAW 264.7 cells. CONCLUSIONS: The present study confirmed that S. alopecuroides had a great potential for accelerated wound healing by regulating the over expression of inflammatory response for the first time and provided theoretical basis for the traditional use. It can be used as candidate drug for the treantment of chronic non-healing wounds.

Scanning electron microscopy of Sophora alopecuroides L. seeds and their cytotoxic, antimicrobial, antioxidant, and enzyme inhibition potentials.

Sophora alopecuroides L. is a highly medicinal plant. The aim of the current study was to determine the phytochemical screening, pharmacological potentials and application of scanning electron microscope (SEM) of S. alopecuroides (SA) seeds. To achieve this purpose, six different solvents were used to prepare SA seed extracts. Phytochemical and antioxidant activities were determined calorimetrically. To investigate the antidiabetic activity, α-amylase inhibition assay was determined. Brine shrimp assay was used to determine cytotoxicity potential. Anti-leishmanial potential was confirmed using MTT assay. Disc-diffusion method was used to detect protein kinase inhibitory, antibacterial and antifungal activities and showed significant results. SEM analysis was used as an identification tool. Considerable amount of phenolic and flavonoid contents were identified in methanol extract (SASM) (93.76 ± 2.71 GAE/mg) and (77 ± 3.60 QE/mg). Highest DPPH scavenging potential (82%) was reported for SASM. Significant total antioxidant capacity (90.60 ± 1.55 alpha amylase enzyme [AAE]/mg) and total reducing power (94.44 ± 1.38 AAE/mg) were determined for LOSM. Highest α-amylase inhibition was reported in SASM (78.20 ± 1.58%). Highest LD50 of brine shrimp was found for n-hexane extract (SASH) 13.03 µg/ml. All extracts showed strong anti-leishmanial activity except SASH. The seeds of SA were seen to be oblong to obovate, projections, wavy slightly straight, anticlinal wall was raised with apex acuminate. In conclusion, our experimental findings highly support the ethnomedicinal and biological potentials of the SA seeds. Moreover, SA seeds need to be explored for identification and isolation of bioactive compounds. In future, we recommend further in vivo toxicity assays and clinical efficacies to further evaluate its different biomedical properties.

Standardization of crude drugs - herb and seeds of Sophora Alopecuroides L / Монголын эм зүй, эм судлал

Introduction@#<i>Sophora alopecuroides L</i> has broadly been utilized in traditional medicine and all crude drugs including root, herb, and seed are used to treat numerous diseases. This herb is included in 181 Tibetan-Mongolian medicinal prescriptions and ranks 8^th among Mongolian medicinal plants in terms of frequency of administration. The <i>S.alopecuroidesL . </i> root standard was developed by the Institute of Traditional Medicine and Technology in 2017 and approved by “ҮФӨ-0307-2017”. Herb and seed are still used in medicine. Therefore, their standard parameters need to be determined and verified.@*Materials and methods@#The quantitative pharmacognosy analysis of herb and seed was carried out in accordance with the methodology specified in the “General requirements for medicinal plant raw materials” of the National Pharmacopoeia of Mongolia. To determine the total alkaloid in standard matrine, a bromcresol green complex was formed, which was measured by spectrophotometer.@*Conclusion@#By developing, standards for the crude drugs of herb and seed of <i>S.alopecuroides L. </i> which are included in numerous medicinal prescriptions, will confirm the rationale for the use of medicinal raw materials and to expand the utilization’s possibilities.

[Association analysis of phenotypic traits of alkaloid content in Sophora alopecuroides with SSR molecular markers].

To further study and fully exploit the medicinal plant Sophora alopecuroides, the molecular markers related with the phenotypic traits of alkaloid content in S. alopecuroides should be detected. In this study, SSR molecular markers were used to analyze the genetic diversity and genetic structure of 23 S. alopecuroides populations, in combination with the association analysis between molecular markers and the alkaloid contents. The results showed that P, H, I, G_(st) and N_m values were 40.10%, 0.335 3, 0.504 5, 0.433 7 and 0.625 9 respectively, in 23 S. alopecuroides populations. This indicated that there was less gene exchange and higher genetic differentiation among different S. alopecuroides populations. The results of SSR unweighted pair-group method with arithmetic means(UPGMA) cluster showed that the S. alopecuroides populations relationship from Xinjiang was far from the populations of other regions, but the populations of S. alopecuroides from Gansu, Inner Mongolia and Qinghai were closely relevant to those from Ningxia. The 23 populations were further divided into 2 genetic subpopulations by the population structure analysis. Through association analysis, a total of 26 loci in 13 SSR markers were found to be significantly associated(P<0.005)with the content of MA, OMA, SC and OSC, and the rate of explanation on the phenotype variance of related markers ranged from 36.45% to 77.93%. Among the locus, 1 each were related with MA and OSC content at interpretation rate reached as high as 50% with high threshold(P<0.000 1). These results could provide support for the discovery of important genes in the alkaloid biosynthetic and metabolic pathway of S. alopecuroides.

Alopecines A-E, five chloro-containing matrine-type alkaloids with immunosuppressive activities from the seeds of Sophora alopecuroides.

Alopecines A-E (1-5), five unusual matrine-type alkaloids featuring with an additional dichlorocyclopropane (1-3) or a di/tri-chloromethyl (4/5) attached on the D ring, were isolated from the seeds of Sophora alopecuroides. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques, and X-ray diffraction analyses or time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Alkaloid 4 exhibited potent inhibitory effects on the proliferation of ConA-induced T lymphocytes or LPS-induced B cells with IC50 value of 3.98 or 3.74 µM, respectively.

Total alkaloids of Sophora alopecuroides L. ameliorated murine colitis by regulating bile acid metabolism and gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L. is one of the most commonly used plants in traditional medicine for the management conditions including inflammatory and gastrointestinal disease. However, the therapeutic mechanism of Sophora alopecuroides L.particularly in inflammatory bowel disease (IBD) remains unclear. AIM OF THE STUDY: To evaluate the treatment effects of total alkaloids of Sophora alopecuroides L. in ulcerative colitis (UC) mice model and explore the therapeutic mechanism of KDZ on UC based on bile acid metabolism and gut microbiota. MATERIALS AND METHODS: Colitis were induced in BALB/c mice by administering 3.5% dextran sulfate sodium (DSS) in drinking water for 7 days. The mice were then given KDZ (300, 150 and 75 mg/kg) and the positive drug sulfasalazine (SASP, 450 mg/kg) via oral administration for 7 days. The levels of 23 bile acids in the liver, bile, serum, cecum content and colon were determined through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The cecum microbiota was characterized through high-throughput Illumina MiSeq sequencing. RESULTS: KDZ treatment significantly decreased the disease activity index (DAI) scores and ameliorated colonic injury in DSS-treated mice. The expression of IL-1ß and TGF-ß1 were suppressed, yet, IL-10 was up-regulated by KDZ and SASP treatment compared with those in the model group. Meanwhile, the serum contents of total bile acid and total cholesterol in the DSS group increased significantly compared with those in the control group, but reversed by SASP and KDZ. The relative abundance of Firmicutes increased after KDZ was administration, whereas the abundance of Bacteroidetes decreased. αMCA, ßMCA, ωMCA and CA in the SASP and KDZ groups did not differ from those in the control group, whereas these parameters significantly increased in the DSS group. CONCLUSIONS: KDZ had a protective effect on DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis and regulating bile acid metabolism.

Aloperine Induces Apoptosis by a Reactive Oxygen Species Activation Mechanism in Human Ovarian Cancer Cells.

BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy worldwide with poor prognosis owing to chemotherapy resistance and cancer relapse. Hence, there is an urgent need to develop novel anticancer agents against ovarian cancer. OBJECTIVE: The aim of this research is to investigate the possible anticancer activity of aloperine, an active ingredient from a traditional Chinese medicine Sophora alopecuroides, and to explore the possible Reactive Oxygen Species (ROS)-related mechanism. METHODS: Cell viability, cytotoxicity, apoptosis, ROS generation, and oxidant stress indicators were analyzed. RESULTS: Our results demonstrated that aloperine significantly induced inhibition of cell viability, promoted cytotoxicity and mitochondrial-related apoptosis, and increased ROS generation in ovarian cancer cells. Furthermore, the antioxidant α-lipoic acid reversed apoptosis in aloperinetreated cells. In addition, we identified hydrogen peroxide as the main type of ROS, and the antioxidant catalase suppressed the apoptotic inducing effect of aloperine whereas hydrogen peroxide supplement exacerbated the effect of aloperine in ovarian cancer cells. CONCLUSION: Taken together, our results indicated that aloperine could exert anti-ovarian cancer cell activity through a reactive oxygen species activation mechanism and suggested aloperine as a potential agent against ovarian cancer.

Pharmacokinetics, Tissue Distribution, and Druggability Prediction of the Natural Anticancer Active Compound Cytisine N-Isoflavones Combined with Computer Simulation.

Cytisine N-methylene-(5,7-dihydroxy-4'-methoxy)-isoflavone (CNF2) is a new compound isolated from the Chinese herbal medicine Sophora alopecuroides. Preliminary pharmacodynamic studies demonstrated its activity in inhibiting breast cancer cell metastasis. This study examined the pharmacokinetics, absolute bioavailability, and tissue distribution of CNF2 in rats, and combined computer-aided technology to predict the druggability of CNF2. The binding site of CNF2 and the breast cancer target human epidermal growth factor receptor-2 (HER2) were examined with molecular docking technology. Next, ACD/Percepta software was used to predict the druggability of CNF2 based on the quantitative structure-activity relationship (QSAR). Finally, a simple and effective HPLC method was used to determine plasma pharmacokinetics and tissue distribution of CNF2 in rats. Prediction and experimental results show that compared with the positive control HER2 inhibitor SYR127063, CNF2 has a stronger binding affinity with HER2, suggesting that its efficacy is stronger; and the structure of CNF2 complies with the Lipinski's Rule of Five and has good drug-likeness. The residence time of CNF2 in rats is less than 4 h, and the metabolic rate is relatively fast; But the absolute bioavailability of CNF2 in rats was 6.6%, mainly distributed in the stomach, intestine, and lung tissues, where the CNF2 contents were 401.20, 144.01, and 245.82 µg/g, respectively. This study constructed rapid screening and preliminary evaluation of active compounds, which provided important references for the development and further research of such compounds.

Efficacy and safety of Sophora alopecuroides var. alopecuroides seed extract for opioid detoxification: A randomized, double-blind, and placebo-controlled clinical trial.

The seeds of Sophora alopecuroides L. var. alopecuroides (S. alopecuroides) have alleviated morphine withdrawal in mice. Therefore, in this study, the alkaloid composition of S. alopecuroides extract was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analysis. Moreover, 50 abstinent opium addicts consumed three 400 mg extract capsules once daily and 50 other patients took placebo for 8 days. At the baseline and days 3 and 8, the clinical opiate withdrawal scale (COWS) was used to assess withdrawal symptoms. At the baseline and Day 8, the patients' blood levels of serum glutamate oxaloacetate transferase; serum glutamate pyruvate transferase; alkaline phosphatase; total, direct, and indirect bilirubins; creatinine and blood urea nitrogen; complete blood count; and prothrombine time were measured. The groups' parameter values were also compared. Sophocarpine, matrine, and sophoramine were the major alkaloids constituting, respectively, 32.85, 26.55, and 6.91% of the extract. The extract decreased the COWS score at Days 3 and 8 significantly compared with the placebo (p < .001). The extract did not significantly affect the blood parameters' values compared with the placebo (p > .05). There was no adverse drug effect. In conclusion, the extract reduces the acute opioid withdrawal symptoms and seems to have good safety and tolerability.

Association analysis of phenotypic traits of alkaloid content in Sophora alopecuroides with SSR molecular markers / 中国中药杂志

To further study and fully exploit the medicinal plant Sophora alopecuroides, the molecular markers related with the phenotypic traits of alkaloid content in S. alopecuroides should be detected. In this study, SSR molecular markers were used to analyze the genetic diversity and genetic structure of 23 S. alopecuroides populations, in combination with the association analysis between molecular markers and the alkaloid contents. The results showed that P, H, I, G_(st) and N_m values were 40.10%, 0.335 3, 0.504 5, 0.433 7 and 0.625 9 respectively, in 23 S. alopecuroides populations. This indicated that there was less gene exchange and higher genetic differentiation among different S. alopecuroides populations. The results of SSR unweighted pair-group method with arithmetic means(UPGMA) cluster showed that the S. alopecuroides populations relationship from Xinjiang was far from the populations of other regions, but the populations of S. alopecuroides from Gansu, Inner Mongolia and Qinghai were closely relevant to those from Ningxia. The 23 populations were further divided into 2 genetic subpopulations by the population structure analysis. Through association analysis, a total of 26 loci in 13 SSR markers were found to be significantly associated(P<0.005)with the content of MA, OMA, SC and OSC, and the rate of explanation on the phenotype variance of related markers ranged from 36.45% to 77.93%. Among the locus, 1 each were related with MA and OSC content at interpretation rate reached as high as 50% with high threshold(P<0.000 1). These results could provide support for the discovery of important genes in the alkaloid biosynthetic and metabolic pathway of S. alopecuroides.

Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora alopecuroides L., which is called Kudouzi in China, is a medicinal plant distributed in Western and Central Asia, especially in China, and has been used for decades to treat fever, bacterial infection, heart disease, rheumatism, and gastrointestinal diseases. AIM OF THE REVIEW: This review aims to provide up-to-date information on S. alopecuroides, including its botanical characterization, medicinal resources, traditional uses, phytochemistry, pharmacological research, and toxicology, in exploring future therapeutic and scientific potentials. MATERIALS AND METHODS: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations, and other web sources, such as the official website of Flora of China and Yao Zhi website (https://db.yaozh.com/). RESULTS: A total of 128 compounds, such as alkaloids, flavonoids, steroids, and polysaccharides, were isolated from S. alopecuroides. Among these compounds, the effects of alkaloids, such as matrine and oxymatrine, were extensively studied and developed into new drugs. S. alopecuroides and its active components had a wide range of pharmacological activities, such as anticancer, antiviral, anti-inflammatory, antimicrobial, analgesic, and neuroprotective functions, as well as protective properties against pulmonary fibrosis and cardiac fibroblast proliferation. CONCLUSIONS: As an important traditional Chinese medicine, modern pharmacological studies have demonstrated that S. alopecuroides has prominent bioactivities, especially on gynecological inflammation and hepatitis B, and anticancer activities. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the comprehensive evaluation, quality control, understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of S. alopecuroides require further detailed research.