Scutellaria baicalensis water decoction ameliorates lower respiratory tract infection by modulating respiratory microbiota.

BACKGROUND: The pathogenesis of lower respiratory tract infections (LRTIs) has been demonstrated to be strongly associated with dysbiosis of respiratory microbiota. Scutellaria baicalensis, a traditional Chinese medicine, is widely used to treat respiratory infections. However, whether the therapeutic effect of S. baicalensis on LRTIs depends upon respiratory microbiota regulation is largely unclear. PURPOSE: To investigate the potential effect and mechanism of S. baicalensis on the respiratory microbiota of LRTI mice. METHODS: A mouse model of LRTI was established using Klebsiella pneumoniae or Streptococcus pneumoniae. Antibiotic treatment was administered, and transplantation of respiratory microbiota was performed to deplete the respiratory microbiota of mice and recover the destroyed microbial community, respectively. High-performance liquid chromatography (HPLC) was used to determine and quantify the chemical components of S. baicalensis water decoction (SBWD). Pathological changes in lung tissues and the expressions of serum inflammatory cytokines, including interleukin-17A (IL-17A), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were determined by hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA), respectively. Quantitative real-time PCR (qRT-PCR) analysis was performed to detect the mRNA expression of GM-CSF. Metagenomic sequencing was performed to evaluate the effect of SBWD on the composition and function of the respiratory microbiota in LRTI mice. RESULTS: Seven main components, including scutellarin, baicalin, oroxylin A-7-O-ß-d-glucuronide, wogonoside, baicalein, wogonin, and oroxylin A, were identified and their levels in SBWD were quantified. SBWD ameliorated pulmonary pathological injury and inflammatory responses in K. pneumoniae and S. pneumoniae-induced LRTI mice, as evidenced by the dose-dependent reductions in the levels of serum inflammatory cytokines, IL-6 and TNF-α. SBWD may exert a bidirectional regulatory effect on the host innate immune responses in LRTI mice and regulate the expressions of IL-17A and GM-CSF in a microbiota-dependent manner. K. pneumoniae infection but not S. pneumoniae infection led to dysbiosis in the respiratory microbiota, evident through disturbances in the taxonomic composition characterized by bacterial enrichment, including Proteobacteria, Enterobacteriaceae, and Klebsiella. K. pneumoniae and S. pneumoniae infection altered the bacterial functional profile of the respiratory microbiota, as indicated by increases in lipopolysaccharide biosynthesis, metabolic pathways, and carbohydrate metabolism. SBWD had a certain trend on the regulation of compositional disorders in the respiratory flora and modulated partial microbial functions embracing carbohydrate metabolism in K. pneumoniae-induced LRTI mice. CONCLUSION: SBWD may exert an anti-infection effect on LRTI by targeting IL-17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation.

Exploring the therapeutic potential of tonic Chinese herbal medicine for gynecological disorders: An updated review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynecological disorders have the characteristics of high incidence and recurrence rate, which sorely affects female's health. Since ancient times, traditional Chinese medicine (TCM), especially tonic medicine (TM), has been used to deal with gynecological disorders and has unique advantages in effectiveness and safety. AIM OF THE REVIEW: In this article, we aim to summarize the research progress of TMs in-vivo and in-vitro, including their formulas, single herbs, and compounds, for gynecological disorders treatment in recent years, and to offer a reference for further research on the treatment of gynecological disorders and their clinical application in the treatment of TMs. MATERIALS AND METHODS: Relevant information on the therapeutic potential of TMs against gynecological disorders was collected from several scientific databases including Web of Science, PubMed, CNKI, Google Scholar and other literature sources. RESULTS: So far, there are 46 different formulas, 3 single herbs, and 24 compounds used in the treatment of various gynecological disorders such as premature ovarian failure, endometriosis breast cancer, and so on. Many experimental results have shown that TMs can regulate apoptosis, invasion, migration, oxidative stress, and the immune system. In addition, the effect of TMs in gynecological disorders treatment may be due to the regulation of VEGF, PI3K-AKT, MAPK, NF-κB, and other signaling pathways. Apparently, TMs play an active role in the treatment of gynecological disorders by regulating these signaling pathways. CONCLUSION: TMs have a curative effect on the prevention and treatment of gynecological disorders. It could relieve and treat gynecological disorders through a variety of pathways. Therefore, the appropriate TM treatment program makes it more possible to treat gynecological disorders.

Mechanistic Role of Scutellaria baicalensis Georgi in Breast Cancer Therapy.

Breast cancer is one of the most common malignancies in women, and exhibits high metastasis, recurrence and fatality rates. Novel therapies for breast cancer are constantly emerging, such as targeted therapy, oncolytic virotherapy, and immunotherapy. Despite their potential, these new therapies are still in their infancy, and chemotherapy remains the standard treatment for breast cancer. Therefore, it is of great significance to develop safe and efficient treatment drugs or adjuvants for breast cancer treatment. Traditional Chinese medicine (TCM) has a long clinical history in China, in which Scutellaria baicalensis Georgi exhibits favorable antibreast cancer activities. We therefore conducted a systematic review of the available literature to better understand the molecular mechanisms of S. baicalensis in breast cancer treatment. S. baicalensis and its active components (baicalein, baicalin, wogonin, wogonoside, oroxylin A and scutellarin) exhibited promising antibreast cancer activity through proliferation inhibition, apoptosis induction, invasion and metastasis blockading, and drug-resistance and non-coding RNA regulation. Additionally, senescence, autophagy, angiogenesis, and glycolysis mechanisms were observed to play a role in their antibreast cancer activity. Furthermore, multiple signaling pathways contributed to the antitumor effects of S. baicalensi, such as the NF-[Formula: see text]B, Wnt/[Formula: see text]-catenin, SATB1, Bcl2 family proteins, Caspase, PI3K/Akt, mTOR, ERK, p38-MAPK, TGF-[Formula: see text]/Smad, and Hippo/YAP pathways. This review provides valuable insights into the role of S. baicalensis as a breast cancer treatment and acts as a foundation for further investigations in this field.

Targeting lncRNAs in programmed cell death as a therapeutic strategy for non-small cell lung cancer.

Lung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the most common histological type. Owing to the limited therapeutic efficacy and side effects of currently available therapies for NSCLC, it is necessary to identify novel therapeutic targets for NSCLC. Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs with a transcript length of more than 200 nucleotides, which play a vital role in the tumorigenesis and progression of multiple cancers, including NSCLC. Induction of programmed cell death (PCD) is the main mechanism leading to tumour cell death in most cancer treatments. Recent studies have demonstrated that lncRNAs are closely correlated with PCD including apoptosis, pyroptosis, autophagy and ferroptosis, which can regulate PCD and relevant death pathways to affect NSCLC progression and the efficacy of clinical therapy. Therefore, in this review, we focused on the function of lncRNAs in PCD of NSCLC and summarized the therapeutic role of targeting lncRNAs in PCD for NSCLC treatment, aiming to provide new sights into the underlying pathogenic mechanisms and propose a potential new strategy for NSCLC therapy so as to improve therapeutic outcomes with the ultimate goal to benefit the patients.

Buxue Yimu Pills improve angiogenesis and blood flow in experimental zebrafish and rat models.

ETHNOPHARMACOLOGICAL RELEVANCE: Buxue Yimu Pills (BYP) is a well-known traditional Chinese medicine prescription which is clinical used in gynecology and obstetrics, and is documented to exhibit therapeutic potential to defective angiogenesis and impaired blood flow. AIM OF THE STUDY: This study aimed to investigate the effects and biological mechanisms of BYP in improvement of defective angiogenesis and impaired blood flow which represent major health issues associated with various diseases including postpartum or abortion complications. MATERIALS AND METHODS: In this study, VEGFR tyrosine kinase inhibitor II (VRI) was used to establish blood vessel loss model in Tg(fli-1a:EGFP) zebrafish embryos. Blood vessel loss was calculated, and quantitative real-time PCR (qRT-PCR) assay was performed to detect gene expression. Mifepristone and misoprostol were applied to construct a medical-induced incomplete abortion rats model. Whole blood viscosity indexes, hemorheology and coagulation function of the rats were investigated. Immunohistochemistry analysis was used for evaluation of the uterine tissues. RESULTS: BYP treatment significantly promoted angiogenesis as evidenced by the restoration of VRI-induced blood vessel loss in zebrafish embryos. BYP treatment effectively reversed VRI-induced down-regulation of the VEGFRs (Kdr, Kdrl and Flt1). Furthermore, BYP administration significantly suppressed the increase of whole blood viscosity indexes, and remarkably shortened the levels of prothrombin time and activated partial thromboplastin time in the medical-induced incomplete abortion rats, indicating the improvement of hemorheology and coagulation function. Immunohistochemistry analysis suggested that BYP administration increased the expression level of VEGFR2 in uterus tissues of the rats. CONCLUSION: BYP exhibits therapeutic effects in promoting angiogenesis and blood circulation, and mitigating blood stasis, supporting its clinical application for postpartum or abortion complications.

Towards a better understanding of Fagopyrum dibotrys: a systematic review.

Fagopyrum dibotrys (F. dibotrys) (D.Don) H.Hara is a well-known edible herbal medicine in Asian countries. It has been widely used for the treatment of lung diseases, swelling, etc., and is also an important part of many Chinese medicine prescriptions. At present, more than 100 compounds have been isolated and identified from F. dibotrys, and these compounds can be primarily divided into flavonoids, phenols, terpenes, steroids, and fatty acids. Flavonoids and phenolic compounds are considered to be the main active ingredients of F. dibotrys. Previous pharmacological studies have shown that F. dibotrys possesses anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, and anti-diabetic activities. Additional studies on functional genes have led to a better understanding of the metabolic pathways and regulatory factors related with the flavonoid active ingredients in F. dibotrys. In this paper, we systemically reviewed the research advances on the phytochemistry and pharmacology of F. dibotrys, as well as the functional genes related to the synthesis of active ingredients, aiming to promote the development and utilization of F. dibotrys.

Assessment of the anti-inflammatory effects of three rhubarb anthraquinones in LPS-Stimulated RAW264.7 macrophages using a pharmacodynamic model and evaluation of the structure-activity relationships.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb (Rhei Radix et Rhizoma) is a traditional Chinese medicine, has been used as a strong astringent in China to treat inflammation-related diseases, such as acute pancreatitis, acute cholecystitis, appendicitis and so on. Rhein, emodin and aloe-emodin are the important active anthraquinone in rhubarb, and are considered to be the main ingredients contributing to anti-inflammatory. AIM OF THE STUDY: Rhein, emodin and aloe-emodin, anthraquinones with the same parent structure that are found in rhubarb, have beneficial anti-inflammatory effects in vitro and in vivo. Anthraquinone derivatives also have important clinical roles. However, their pharmacodynamic differences and the structure-activity relationships associated with their anti-inflammatory properties have not been systematically explored. The present study was designed to quantify the effects of three rhubarb anthraquinones on inflammation and to explore the structure-activity relationships of these compounds. MATERIALS AND METHODS: In this study, we detected NF-κB phosphorylation, iNOS protein expression, and IL-6 and NO production in LPS-stimulated RAW264.7 cells and then calculated median effect equations and built a dynamic pharmacodynamic model to quantitatively evaluate the efficacy of these three anthraquinones. Additionally, to determine the structure-activity relationships, we investigated the physicochemical properties and molecular electrostatic potentials of the drug molecules. RESULTS: We found that rhein, emodin, and aloe-emodin exerted at least dual-target (NF-κB, iNOS) inhibition of LPS-induced inflammatory responses. Compared with rhein and emodin, aloe-emodin had a stronger anti-inflammatory effect, and its inhibition of iNOS protein expression was approximately twice that of NF-κB phosphorylation. In addition, aloe-emodin had the strongest hydrophobic effect among the three anthraquinones. CONCLUSIONS: Overall, we concluded that the receptor binding the rhubarb anthraquinones had a hydrophobic pocket. Anthraquinone molecules with stronger hydrophobic effects had higher affinity for the receptor, resulting in greater anti-inflammatory activity. These results suggest that the addition of a hydrophobic group is a potential method for structural modification to design anti-inflammatory anthraquinone derivatives with enhanced potency.

Coptisine from Coptis chinensis exerts diverse beneficial properties: A concise review.

Coptisine is a natural small-molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as 'coptisine' in combination of 'each pivotal pathway target'. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti-cancer, anti-inflammatory, CAD ameliorating or anti-bacterial drug through regulating the signalling transduction of pathways such as NF-κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non-liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase-1-involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano- or microrods strategies or applying salt-forming process to coptisine, can it be introduced to clinical trial.

Pharmacokinetic-Pharmacodynamic Modeling for Coptisine Challenge of Inflammation in LPS-Stimulated Rats.

Pro-inflammatory factors are important indicators for assessing inflammation severity and drug efficacy. Coptisine has been reported to inhibit LPS-induced TNF-α and NO production. In this study, we aim to build a pharmacokinetic-pharmacodynamic model to quantify the coptisine time course and potency of its anti-inflammatory effect in LPS-stimulated rats. The plasma and lung coptisine concentrations, plasma and lung TNF-α concentrations, plasma NO concentration, and lung iNOS expression were measured in LPS-stimulated rats after intravenous injection of three coptisine doses. The coptisine disposition kinetics were described by a two-compartment model. The coptisine distribution process from the plasma to the lung was described by first-order dynamics. The dynamics of plasma TNF-α generation and elimination followed zero-order kinetics and the Michaelis-Menten equation. A first-order kinetic model described the TNF-α diffusion process from the plasma to the lung. A precursor-pool indirect response model was used to describe the iNOS and NO generation induced by TNF-α. The inhibition rates of TNF-α production by coptisine (54.73%, 26.49%, and 13.25%) calculated from the simulation model were close to the decline rates of the plasma TNF-α AUC (57.27%, 40.33%, and 24.98%, respectively). Coptisine suppressed plasma TNF-α generation in a linear manner, resulting in a cascading reduction of iNOS and NO. The early term TNF-α response to stimulation is a key factor in the subsequent inflammatory cascade. In conclusion, this comprehensive PK-PD model provided a rational explanation for the interlocking relationship among TNF-α, iNOS and NO production triggered by LPS and a quantitative evaluation method for inhibition of TNF-α production by coptisine.