Cnidii Fructus: A traditional Chinese medicine herb and source of antiosteoporotic drugs.

BACKGROUND: Osteoporosis (OP) is a prevalent chronic metabolic bone disease for which limited countermeasures are available. Cnidii Fructus (CF), primarily derived from Cnidium monnieri (L.) Cusson., has been tested in clinical trials of traditional Chinese medicine for the management of OP. Accumulating preclinical studies indicate that CF may be used against OP. MATERIALS AND METHODS: Comprehensive documentation and analysis were conducted to retrieve CF studies related to its main phytochemical components as well as its pharmacokinetics, safety and pharmacological properties. We also retrieved information on the mode of action of CF and, in particular, preclinical and clinical studies related to bone remodeling. This search was performed from the inception of databases up to the end of 2022 and included PubMed, China National Knowledge Infrastructure, the National Science and Technology Library, the China Science and Technology Journal Database, Weipu, Wanfang, the Web of Science and the China National Patent Database. RESULTS: CF contains a wide range of natural active compounds, including osthole, bergapten, imperatorin and xanthotoxin, which may underlie its beneficial effects on improving bone metabolism and quality. CF action appears to be mediated via multiple processes, including the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK), Wnt/ß-catenin and bone morphogenetic protein (BMP)/Smad signaling pathways. CONCLUSION: CF and its ingredients may provide novel compounds for developing anti-OP drugs.

Simiao San alleviates hyperuricemia and kidney inflammation by inhibiting NLRP3 inflammasome and JAK2/STAT3 signaling in hyperuricemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Simiao San (SmS), a famous traditional Chinese formula, is clinically used to treat patients with hyperuricemia (HUA). However, its mechanism of action on lowering uric acid (UA) and inhibiting inflammation still deserves further investigation. AIM OF THE STUDY: To examine the effect and its possible underlying mechanism of SmS on UA metabolism and kidney injury in HUA mouse. MATERIALS AND METHODS: The HUA mouse model was constructed with the combined administration of both potassium oxalate and hypoxanthine. The effects of SmS on UA, xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by ELISA or biochemical assays. Hematoxylin and eosin (H&E) was used to observe pathological alterations in the kidneys of HUA mice. The expression levels of organic anion transporter 1 (OAT1), recombinant urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), nucleotide binding domain and leucine rich repeat pyrin domain containing 3 (NLRP3), Cleaved-Caspase 1, apoptosis-associated speck like protein (ASC), nuclear factor kappa-B (NF-κB), IL-6, janus kinase 2 (JAK2), phosphor (P)-JAK2, signal transducers and activators of transcription 3 (STAT3), P-STAT3, suppressor of cytokine signaling 3 (SOCS3) were examined by Western blot and/or immunohistochemical (IHC) staining. The major ingredients in SmS were identified by a HPLC-MS assay. RESULTS: HUA mouse exhibited an elevation in serum levels of UA, BUN, CRE, XOD, and the ratio of urinary albumin to creatinine (UACR), and a decline in urine levels of UA and CRE. In addition, HUA induces pro-inflammatory microenvironment in mouse, including an increase in serum levels of IL-1ß, IL-6, and TNF-α, and renal expressions of URAT1, GULT9, NLRP3, ASC, Cleaved-Caspase1, P-JAK2/JAK2, P-STAT3/STAT3, and SOCS3, and a decrease in serum IL-10 level and renal OAT1 expression as well as a disorganization of kidney pathological microstructure. In contrast, SmS intervention reversed these alterations in HUA mouse. CONCLUSION: SmS could alleviate hyperuricemia and renal inflammation in HUA mouse. The action mechanisms behind these alterations may be associated with a limitation of the NLRP3 inflammasome and JAK2/STAT3 signaling pathways.

Majie Cataplasm Promotes Th1 Response to Fight against Asthmatic Th2 Inflammation through NKs.

Background: Immune cells are tightly bound up with the pathogenesis of asthma. Besides T cells, B cells, macrophages, and mast cells, the mechanism of innate lymphoid cells (ILCs) in asthma is gradually explicit. As a kind of traditional Chinese medicine, Majie cataplasm realizes its potential in the clinical setting as an adjuvant for asthma. In our previous experiments, Majie cataplasm inhibits the increasing Th1 and Th2 in allergic asthma inflammation and reshapes a balance between Th1 and Th2. As ILCs are the reflection of Th cells in lung tissues, we will figure out whether Majie cataplasm could have similar effects on ILCs or not. Methods: A total of 40 female C57/BL6 mice were randomly divided into the control group (n = 10), the asthma model group (n = 10), the dexamethasone group (n = 10), and the Majie cataplasm group (n = 10). Except for the control group, mice were sensitized with ovalbumin (OVA) and excited to establish mice models of asthma. Lung tissue and splenic tissue were collected at 24 h after the last challenge with OVA, and the cell suspension of the lungs and spleen was prepared. The number of ILC1s, ILC2s, ILC3s, and NKs cells in the lungs and Tregs and B10s in the spleen were detected by flow cytometry (FCM). This was followed by simultaneous quantitative detection of 40 inflammatory cytokines and chemokines in the lung by a protein microarray. Results: The dexamethasone and Majie cataplasm could restore the number of ILC1s, ILC2s, and ILC3s in lung tissue. Compared with the control group, these cells remained unchanged in the asthma model group, while ILC1s (P < 0.001, P < 0.01), ILC2s (P < 0.001, P < 0.01), and ILC3s (P < 0.01, P < 0.05) were restored after the intervention of dexamethasone and Majie cataplasm. The number of NKs was low among the control group, the asthma model group, and the dexamethasone group, while the number of NKs rocketed in the Majie cataplasm group (P < 0.0001). For splenic Tregs and B10s, Majie cataplasm could curb the increasing numbers of them in the asthma model group (P < 0.0001, P < 0.01), while only Tregs were suppressed by the dexamethasone (P < 0.0001). For the inflammatory cytokines in the lung, the contents of TNF-α, TNFR2, CXCL-9, CCL-12, CCL-9, CCL-2, and CCL-5 in the asthma model group were higher than those in the control group, while the contents of GM-CSF and IL-1α were decreased. Comparing the asthma model group to the dexamethasone group, the levels of G-CSF, CCL-9, CCL-5, and TNFR2 in the former group were higher. The levels of TNF-α, TNFR2, and CCL-9 in the asthma model group increase, while the levels of IFN-γ, IL-1α, ICAM-1, and IL-4 increased in the Majie cataplasm group, especially IFN-γ and IL-1α. Conclusion: Both the dexamethasone and Majie cataplasm could control the asthmatic inflammation by reducing the inflammatory factors, inhibiting the adaptive inflammation reaction in the latter stage of inflammation and furtherly reversing the inhibition of ILC2s, ILC2s, and ILC3s. In addition, Majie cataplasm can promote the quantity of NKs and the content of IL-1α and IFN-γ, induce IFN-γ +NKs to shut down the Th2 response, and tend to elicit the Th1 response.

The mediatory role of Majie cataplasm on inflammation of allergic asthma through transcription factors related to Th1 and Th2.

BACKGROUND: Asthma, a common respiratory disease, is harmful biological effect to our health. As a traditional Chinese medicine for asthma, Majie cataplasm could alleviate the symptoms of asthma and its compositions have immunomodulatory effects. Previous experiments showed that Majie cataplasm was an effective approach to mitigate asthma airway remodeling and had the potential to regulate Th2 cytokines of IL-5 and IL-13. Therefore, our further research focuses on the explanation about the regulatory effect of Majie cataplasm on reshaping Th1/Th2 through their related transcription factors. METHODS: In this experiment, the launch of asthma model was made by inducing with Ovalbumin (OVA) in C57 mice (n = 40), including 4 groups: the untreated control group (n = 10), the asthma model group (n = 10), the dexamethasone group (n = 10) and the Majie cataplasm group (n = 10). After the intervention, all groups of animals got detected for serum IgE levels, and HE staining of lung tissues was to observe and examine pathological changes. Meanwhile, we analyzed the secretion of IL-4+ T cells and IFN-γ+ T cells in spleen by flow cytometry. The expressions of transcription factor STAT6 mRNA, GATA-3 mRNA and T-bet mRNA in lung tissues was tested by PCR, and western blot had been used to detect levels of JAK2 and STAT3. RESULTS: We found that Majie cataplasm eased the content of serum IgE and lung inflammation. It could lower the increased number of IL-4+ T cells and IFN-γ+ T cells (P < 0.0001, P < 0.01) in asthmatic mice and curb the expression of STAT6 mRNA and GATA-3 (P < 0.0001, P < 0.01) mRNA as well as the protein levels of JAK2 (P < 0.001) and the ratio of pSTAT3/STAT3 (P < 0.05). Besides, Majie cataplasm made its mark on T-bet mRNA by improving it (P < 0.0001). CONCLUSION: These data suggest that Majie cataplasm exert an anti-inflammatory effect of Th2 by rebalancing Th1/Th2 through corresponding transcription factor STAT6, GATA-3, STAT3, and T-bet, which providing a strong cornerstone for asthma control.

[Study on famous prescription of prestigious traditional Chinese medicine based on QbD concept: optimization of extraction process and granule forming process of Tuomin Dingchuan Prescription].

The quality of compound traditional Chinese medicine is the prerequisite and foundation for its stable efficacy. Based on the quality by design( QbD) concept,the controllable extraction times,extraction time and the ratio of water were the critical process parameters( CPPs) in the Tuomin Dingchuan Prescription extraction process. The CQAs corresponding to CPPs were screened from the four potential critical quality attributes( p CQAs),namely the extraction amount of solid matter,the content of amygdalin,the content of cimicifugoside and the content of 5-O-methylvisammioside by orthogonal experiment. The extraction amount of solid matter and the content of amygdalin were determined as CQAs in the extraction process by the variance analysis of Box-Behnken experimental. The optimal extraction process based on the linear model between CQAs and CPPs of the extraction process was immersion in water for 30 minutes,extraction for three times,extraction for 100 minutes each time and 10 times of water volume. The control space was established for the extraction amount of solid matter and the content of amygdalin,and both of them could be controlled simultaneously to achieve the optimization objective. The molding ratio of Tuomin Dingchuan granules was regarded as CQA in forming process. On the basis of the single factor investigation,the ratio of dry extract powder to excipient and the ratio of ethanol were determined as CPPs. The central composite design( CCD) was used to optimize the forming process of Tuomin Dingchuan granules. The results showed that the dextrin was used as the filler; the ratio of dry paste to dextrin was 1 ∶1; and 0. 3 m L·g-1 of 70% ethanol was added as binder. The soft material and granules conformed to the actual production requirements.