Journal of Holistic Integrative Pharmacy最新文献

Objective

To investigate the functional genes involved in the lignans biosynthesis in Saururus chinensis.

Methods

An RNA-Seq based tissue-specific comparative transcriptome analysis of S. chinensis leaves and rhizomes was performed, and an up-to-date bioinformatical analysis was carried out to discover the candidate functional genes. mRNA expression of part of the candidate genes were confirmed by qRT-PCR.

Results

According to the De novo transcriptome assembly, 49 430 unigenes in S. chinensis were presented and 33 222 unigenes (67.21%) were functionally annotated. Successively, 13 031 (26.36%) differentially expressed genes were filtered, and then GO and KEGG classification and enrichment analysis combined Swissprot function prediction revealed twenty-eight candidate genes encoding twelve enzymes involved in lignans biosynthesis pathways. The qRT-PCR results were consistent with the RNA-Seq analysis for the candidate genes.

Conclusion

These results enrich our knowledge on lignans biosynthesis-related functional genes and facilitate further synthetic biology research on specific lignans in S. chinensis.

Objective

To investigate whether Acori Graminei Rhizoma (AGR) volatile oil can reduce inflammatory pain-induced pain-related mood in rats by downregulating NMDARs-ERK 1/2-CREB signaling pathway.

Methods

Thirty-six male SD rats were randomly divided into six groups: control group, sham group, complete Freund's adjuvant (CFA) group, CFA + 0.1 mL/10 g volatile oil group, CFA + 0.2 mL/10 g volatile oil group, and CFA + 0.4 mL/10 g volatile oil group. Six rats in each group were gavaged for 21 days and tested for mechanical pain hypersensitivity and positional avoidance (PEAP) before and after drug treatment. In addition, another batch of thirty-six male SD rats were randomly divided into six groups, including control, sham, CFA, CFA + saline, CFA + 0.1 mg/kg NMDA, and CFA + 0.1 mg/kg Ifenprodil groups. The control group did not receive any treatment, and the sham group received the same volume of sterile saline at the same site. Animals in each group were tested for mechanical pain hypersensitivity and positional avoidance before and after drug treatment. The expression levels of NMDAR1, NMDAR2A, NMDAR2A2B, mGlur1, ERK 1/2, CREB, and c-Fos in the basolateral amygdala (BLA) were determined by immunofluorescent staining and Western blot methods.

Results

AGR essential oil could reduce mechanical hyperalgesia and position avoidance in animals caused by CFA, and down-regulate NMDARs, mGlur1/5, ERK 1/2 and CREB expression. While up-regulation of c-Fos expression by NMDAR inhibitor Ifenprodil, reversed the above phenomena.

Conclusion

AGR essential oil alleviates inflammatory pain-induced pain-related mood in rats through downregulation of the NMDARs-ERK1/2-CREB signaling pathway.

Objective

The clinical treatment rules and mechanism of Alismatis Rhizoma prescription for hyperlipidemia treatment were analyzed based on data mining and network pharmacology.

Methods

The CNKI, Wanfang, and PubMed databases were searched to collect the prescriptions containing Alismatis Rhizoma for the treatment of hyperlipidemia, and the Apriori algorithm was employed to mine the hidden drug compatibility rules and drug pairs in each prescription. The chemical components and target information of drug pairs were analyzed using the TTCMSP, PubChem, and SwissTargetPrediction databases, and the disease targets were screened using the DrugBank database. The intersection of the two was also obtained. Cytoscape was employed to obtain the core targets of the prescription for the treatment of hyperlipidemia, and then the KEGG pathway of the intersection targets was enriched and analyzed using the DAVID database. Molecular docking of core chemical components and key targets and visualization of the docking results were performed using AutoDock and the Discovery Studio 2016 Client platform, respectively. Finally, it was verified by in vitro cell experiments.

Results

The drug pair with the highest support was hawthorn–Salvia miltiorrhiza–Alismatis Rhizoma. This pair contained 112 active components, 384 targets highly correlated with the active components, 111 targets related to hyperlipidemia, and 45 intersection targets of drugs and diseases. Biological function and target pathway enrichment analysis revealed that the biological process of hawthorn–Salvia miltiorrhiza–Alismatis Rhizoma in the treatment of hyperlipidemia was mainly related to steroid metabolism, drug reaction, and redox process. The results of in vitro experiments indicated that Alisol A could reduce cell lipid accumulation and total cholesterol (TC) and TG levels, upregulate of ABCB1 and downregulate of CYP1A2, CYP3A4, and SLC6A4 mRNA expression.

Conclusion

Network pharmacology analysis revealed that the hawthorn–Salvia miltiorrhiza–Alismatis Rhizoma herb pair can treat hyperlipidemia through multiple targets and pathways, which provide a basis for further study of traditional Chinese medicine in the treatment of hyperlipidemia.

Objective

To observe the effects of ursolic acid (UA) on the apoptosis, autophagy and mTOR of human colorectal cancer (CRC) cells resistant to 5-FU (HCT-8/5-FU), and explore the mechanisms of UA reversing the multidrug resistance (MDR) of CRC.

Methods

HCT-8 cells and its resistant cells to 5-FU (HCT-8/5-FU) were cultured to calculate the resistant index and confirmed the resistance of HCT-8/5-FU. The MTT assays were used to screen the suitable concentrations and the reversal fold of UA. The efflux function, proliferation, apoptosis, autophagy and their correlated proteins were determined through Doxorubucin staining, Rhodamine 123 staining, colony formation, Annexin V-PI double staining, Cyto-ID staining and Western blot after the HCT-8/5-FU were intervened with UA for 48 h.

Results

HCT-8/5-FU cells are resistant to different chemotherapeutics, UA could reverse the MDR effectively. Furtherly, UA down-regulates the expression of ABCB1, ABCG2, p62, up-regulates Bax/Bcl-2 and LC3II/LC3I to inhibit the drug-efflux (P<0.05) and induce the apoptosis (P<0.05) and autophagy (P<0.05) via inhibiting the phosphorylation of mTOR.

Conclusion

UA induces the apoptosis and autophagy, blocks the proliferation of HCT-8/5-FU cells via inhibiting the phosphoralation of mTOR, that maybe the important mechanism by which UA reverses the MDR of CRC.

Objective

To investigate pyroptosis in the trophoblast cells HTR-8/Svneo induced by TET2 in oxidized low-density lipoprotein (oxLDL).

Methods

HTR-8/Svneo cells were treated with vehicle (0 mg/L) and 50 mg/L oxLDL for 24 h. The effects of oxLDL on TET2 expression in HTR-8/Svneo cells were detected by Western blot. Knockdown of TET2 was performed in HTR-8/Svneo cells using si-TET2. CCK8, Transwell, and wound healing assays were used to detect the effect of TET2 knockdown on the proliferation, cell cycle, migration, and invasion of HTR-8/Svneo cells, respectively. Western blot was used to quantify the expression levels of the pyroptosis proteins GSDMD and caspase-1 in si-TET2 treated cells.

Results

oxLDL downregulates TET2 expression in a concentration-dependent manner. TET2 knockdown inhibits HTR-8/Svneo invasion and migration but promotes cell proliferation. Western blot results showed that TET2 knockdown upgregulated the expression of GSDMD and caspase-1.

Conclusion

oxLDL induces pyroptosis of HTR-8/Svneo by downregulating TET2 expression, resulting in decreased trophoblast invasion and migration. These data suggest that TET2-induced pyroptosis play a critical role in gestational pathologies, such as preeclampsia. Further studies can clarify the mechanisms of this process and elucidate potential preventive and therapeutic targets.

Objective

To observe the protective effect of Buyang Huanwu decoction (BYHWD) against retinal inflammation in diabetic rats.

Methods

Healthy male Wistar rats were randomly divided into normal and diabetic model groups. Diabetic rats were given a one-time intraperitoneal injection of streptozotocin (STZ) to establish a diabetic phenotype and were randomly assigned to the negative control (saline), positive control (calcium dobesilate), and BYHWD treatment groups. After 8 weeks of treatment, fluorescein-labeled dextran and Evans blue dye were injected into the tail vein to observe vascular permeability and vascular leakage in the retina, respectively. Perfusion of fluorescein-labeled concanavalin was used to detect adhesion in rat retinal leukocytes. Western blotting was used to quantify the expression levels of the inflammatory factors TNF-α, NF-κBp65, and p-NF-κBp65 in retinal tissue.

Results

Compared with nondiabetic rats, saline-treated diabetic rats showed significantly increased retinal vascular leakage, leukocyte adhesion, and protein levels of TNF-α and p-NF-κBp65 (P<0.05). These effects were significantly reduced in the positive control and BYHWD groups (P<0.05).

Conclusion

Buyang Huanwu decoction can ameliorate retinal inflammation in STZ-induced diabetic rats. Its mechanism of action may be related to the inhibition of TNF-α expression and NF-κB pathway activation.

Objective

To explore the main active components and potential targets of “Sanhuang Xiexin decoction” (Sanhuang) against acne based on network pharmacology and molecular docking technology, and research the bacteriostatic mechanism by biochemical experiments.

Methods

Pharmacological database and Analysis platform of the Traditional Chinese Medicine System (TCMSP) and SwissTarget database were used to obtain the active components and the targets of Sanhuang in the treatment of acne, respectively. The acne-related targets were screened by OMIM, GeneCards, and DisGeNET databases, and the interaction targets were analyzed by Cytoscape and String databases, followed with enrichment analysis by Genome Encyclopedia (KEGG) and Gene Ontology (GO). The predicted results were validated by molecular docking. The bacteriostatic zones of Sanhuang to acne were determined by Oxford cup method, and the minimum bacteriostasis concentration was obtained by double dilution method. The bacteria morphology change in the presence of Sanhuang was observed by scanning electron microscope and the ionic leakage rate was detected to reflect the permeability of bacterial cell walls. Finally, the IL-6 expression of drug-treated acne was determined.

Results

From Rheum palmatum L, Coptis chinensis Franch, and Scutellaria baicalensis Georgi, 34, 25 and 44 active ingredients were selected, and 145, 216 and 163 compound targets were screened out, respectively. There are 123 intersection targets of Sanhuang and acne, which mainly function through IL-17, MAPK, PI3K-Akt, and TNF signaling pathways. Molecular simulation results showed that aloe-emodin and quercetin in Coptis Chinensis Franch had strong affinities with the core targets of TNF, IL-6, INS, and AKT1. The antibacterial zones of Sanhuang at concentrations of 0.1 g/mL and 0.5 g/mL were (21.0±0.3) mm and (26.1±0.9) mm, respectively, which had an obvious dose-dependent relationship. The minimum inhibitory concentration of Sanhuang was 4 mg/mL. Moreover, in the drug-treated acne, the morphology of bacterial cells was destroyed, the permeability of cell walls was increased, and the growth of propionibacterium acnes was inhibited. The results of cell experiment showed that Sanhuang inhibited the expression of IL-6.

Conclusion

Based on network pharmacology method, we predicted the mechanism of Sanhuang in the treatment of acne which was charactered by multi-component, multi-target, and multi-pathway, and verified the therapeutic effect of Sanhuang on acne by the biochemical method such as bacteriostasis test and cell experiment. Sanhuang can inhibit the growth of Propionibacterium acnes mainly by regulating the target genes such as TNF, IL-6, INS, and AKT1.

The process of cardiomyocyte death is triggered by prolonged ischemia in the heart during myocardial infarction (MI). And the role of non-coding RNAs in the pathophysiology of cardiovascular diseases has become increasingly important in recent years. RNA molecules known as microRNAs (miRNAs) are small non-coding RNAs whose expression varies across organs. microRNAs play an important role in processes associated with autophagy, which contribute to the development of heart failure. These processes include mitochondrial integrity and function, antioxidant defense, oxidative stress, iron overload, ferroptosis, and survival pathways. microRNAs may serve as promising biomarkers and useful targets in the treatment of cardiovascular disease. For the development of new targeted drugs, it is vital to uncover how microRNA expression changes and how they regulate autophagy. In order to comprehend the mechanisms of myocardial infarction and ischemic reperfusion injury, it is crucial to understand how these two processes relate to each other. In this review, we will provide a brief introduction to microRNAs, autophagy, and associated medicine to microRNAs.

Objective

This study aims to investigate the potential mechanisms underlying motor learning dysfunction in hepatic encephalopathy (HE) mice using gut microbiota and neurochemicals.

Methods

C57BL/6 mice were intraperitoneally treated with thioacetamide to induce the HE model. Cytokines of TNF-α and ammonia in serum and motor cortex were tested using the ELISA kit. Rota-rod was used to assess the motor learning behavior of HE mice. The 16S rDNA analysis revealed gut microbiota species and abundance changes in HE mice. The 26 neurochemicals of control and HE mice were quantified and analyzed with different microbiota using the UPLC-TQ-MS technique.

Results

LEfSe analysis revealed that 25 genera differed significantly between healthy and HE mice. Correlation analysis revealed that the Escherichia_Shigella, Allobaculum, and Muribaculaceae were associated with higher adrenaline levels of hydrochloride, 4-aminobytyric acid, and L-glutamic acid and lower levels of L-histidine and histamine.

Conclusion

The neurotransmitter changes in motor cortex have some relationship with gut microbiota disturbances. This correlation may pave the way to explain the cognitive and motor learning dysfunction in HE mice.

Objective

This study aimed to compare the antibacterial performance of 18 natural plants against six types of microorganisms that tend to grow in cosmetics and select the best natural antiseptic herbs with low toxicity and a broad antibacterial spectrum. The safety performance and effects of the antioxidant, whitening, and reduced inflammation of Coptis chinensis fermentation were explored.

Methods

The inhibition performance of the alcoholic extracts for the 18 natural plants against six microorganisms was compared by using the cylinder plate method. The MTT assay was used to determine the cell viability of C. chinensis extract and fermentation products. DPPH, hydroxyl, and ABTS radical scavenging rates as well as iron reduction ability were used to evaluate the antioxidant efficacy. In addition, the activity inhibition rate of tyrosinase and hyaluronidase indicated the whitening and anti-inflammatory properties of C. chinensis extract and fermentation broth.

Results

Results showed that among the 18 natural plants, C. chinensis extract had the most prominent inhibition circles and the smallest minimum inhibitory concentration (MIC) value against six microorganisms. After fermentation, the IC₅₀ value of C. chinensis alcoholic extract increased significantly with the cell survival rate, indicating its low biosafety. The free radical scavenging rate, tyrosinase inhibition rate, and hyaluronidase inhibition rate of fermented C. chinensis extract increased significantly, showing better antioxidant activity, whitening activity, and anti-inflammatory activity than alcohol extract.

Conclusion

Among the 18 natural plants, C. chinensis has the most substantial antibacterial ability. After fermentation by yeast, the cytotoxicity of C. chinensis decreases, and the antioxidant, whitening, and anti-inflammatory activities increase, indicating that microbial fermentation attenuates toxicity and enhances the effect of plant preservatives.