Cavidine

Banxia-Shengjiang drug pair inhibits gastric cancer development and progression by improving body immunity.[Pubmed:38457601]

Medicine (Baltimore). 2024 Mar 8;103(10):e36303.

To investigate the mechanism of action of Banxia-Shengjiang drug pair on the inhibition of gastric cancer (GC) using network pharmacology and bioinformatics techniques. The action targets of the Banxia (Pinellia ternata (Thunb.) Makino) -Shengjiang (Zingiber officinale Roscoe) drug pair obtained from the TCMSP database were intersected with differentially expressed genes (DEGs) and GC-related genes, and the intersected genes were analyzed for pathway enrichment to identify the signaling pathways and core target genes. Subsequently, the core target genes were analyzed for clinical relevance gene mutation analysis, methylation analysis, immune infiltration analysis and immune cell analysis. Finally, by constructing the PPI network of hub genes and corresponding active ingredients, the key active ingredients of the Banxia-Shengjiang drug pair were screened for molecular docking with the hub genes. In this study, a total of 557 target genes of Banxia-Shengjiang pairs, 7754 GC-related genes and 1799 DEGs in GC were screened. Five hub genes were screened, which were PTGS2, MMP9, PPARG, MMP2, and CXCR4. The pathway enrichment analyses showed that the intersecting genes were associated with RAS/MAPK signaling pathway. In addition, the clinical correlation analysis showed that hub genes were differentially expressed in GC and was closely associated with immune infiltration and immunotherapy. The results of single nucleotide variation (SNV) and copy number variation (CNV) indicated that mutations in the hub genes were associated with the survival of gastric cancer patients. Finally, the PPI network and molecular docking results showed that PTGS2 and MMP9 were potentially important targets for the inhibition of GC by Banxia-Shengjiang drug pair, while Cavidine was an important active ingredient for the inhibition of GC by Banxia-Shengjiang drug pair. Banxia-Shengjiang drug pair may regulate the immune function and inhibit GC by modulating the expression of core target genes such as RAS/MAPK signaling pathway, PTGS2 and MMP9.

[Research progress of Shegan Mahuang Decoction and predictive analysis on its Q-markers].[Pubmed:37282895]

Zhongguo Zhong Yao Za Zhi. 2023 Apr;48(8):2068-2076.

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, Cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment.[Pubmed:36897671]

Medicine (Baltimore). 2023 Mar 10;102(10):e33229.

Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that Cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of Cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.

Exploring the Latent Mechanism of Huanglian Jiedu Decoction Formula for Anti-atopic Dermatitis by Systems Pharmacology.[Pubmed:35642108]

Comb Chem High Throughput Screen. 2023;26(3):610-629.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease, which does not have a specific drug presently. Huanglian jiedu decoction (HJD) is one of the effective traditional Chinese medicine prescriptions. The real material and mechanisms of HJD for AD are not clear. OBJECTIVE: Network pharmacology and in vivo experiments were used to explore the real material and mechanisms of HJD for AD. METHODS: A systems' pharmacology approach that provides a comprehensive analysis of bioactive compounds, targets, and pathway interactions was employed to elucidate the molecular pathogenesis of HJD for AD. First, the compound databases were constructed for HJD, and compound targets were predicted. Then, the hub targets of HJD were selected by degree centrality analysis and validated using the molecular docking method. Finally, Compound-Target and Target-Pathway networks were constructed to explore the latent mechanism of HJD for AD. Then, animal models of AD were established, the pathology of the skin lesions was observed, and RT-PCR and ELISA methods were used to verify the key targets in the serum of AD mice. RESULTS: The results showed that 60 bioactive compounds (palmatine, wogonin, Cavidine, etc.) of HJD interacting with 169 related hub targets (PTGS2, HSP90AA1, etc.) were authenticated. HJD potentially participates in response to stimuli, biological regulation, and reproduction through the PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and Fc epsilon RI signaling pathway, which are interrelated to the pathogenesis of AD. Compared with the control group, the thickening of the epidermis in the model group was obvious with inflammatory cells infiltrating, the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-alpha were up-regulated; and 6.4g/kg and 12.8g/kg HJD could significantly reduce the thickening of the epidermis and infiltration of inflammatory cells, down-regulate the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-alpha in the AD mice. HJD might exert its anti-AD effects by downregulating key indicators (PI3K, AKT, JNK, ERK, IL-4, and TNF-alpha) in the PI3K/AKT and MAPK pathways. CONCLUSIONS: Our study could help us understand the compound and mechanism of HJD for AD. Moreover, it had a guidance function to change the traditional arrangement of formula for HJD.

The genome of Corydalis reveals the evolution of benzylisoquinoline alkaloid biosynthesis in Ranunculales.[Pubmed:35476217]

Plant J. 2022 Jul;111(1):217-230.

Species belonging to the order Ranunculales have attracted much attention because of their phylogenetic position as a sister group to all other eudicot lineages and their ability to produce unique yet diverse benzylisoquinoline alkaloids (BIAs). The Papaveraceae family in Ranunculales is often used as a model system for studying BIA biosynthesis. Here, we report the chromosome-level genome assembly of Corydalis tomentella, a species of Fumarioideae, one of the two subfamilies of Papaveraceae. Based on comparisons of sequenced Ranunculalean species, we present clear evidence of a shared whole-genome duplication (WGD) event that has occurred before the divergence of Ranunculales but after its divergence from other eudicot lineages. The C. tomentella genome enabled us to integrate isotopic labeling and comparative genomics to reconstruct the BIA biosynthetic pathway for both sanguinarine biosynthesis shared by papaveraceous species and the Cavidine biosynthesis that is specific to Corydalis. Also, our comparative analysis revealed that gene duplications, especially tandem gene duplications, underlie the diversification of BIA biosynthetic pathways in Ranunculales. In particular, tandemly duplicated berberine bridge enzyme-like genes appear to be involved in Cavidine biosynthesis. In conclusion, our study of the C. tomentella genome provides important insights into the occurrence of WGDs during the early evolution of eudicots, as well as into the evolution of BIA biosynthesis in Ranunculales.

Inhibitory and inductive effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cytochrome P450s in rats.[Pubmed:29806105]

Phytother Res. 2018 Sep;32(9):1818-1827.

Corydalis saxicola Bunting, a well-known traditional Chinese medicine in south China, has been widely used for the treatment of various hepatic diseases. Its active ingredients are Corydalis saxicola Bunting total alkaloids (CSBTA), which primarily include dehydroCavidine, palmatine, and berberine. These representative alkaloids could be metabolized by hepatic CYP450s. Hence, it is necessary to investigate the potential influences of CSBTA on CYP450s to explore the possibility of herb-drug interactions. In present study, in vitro inhibition and in vivo induction studies were performed to evaluate the potential effects of CSBTA extract on CYP450s in rats. Inhibition assay illustrated that CSBTA exerted inhibitory effects on CYP1A2 (IC(50) , 38.08 mug/ml; K(i) , 14.3 mug/ml), CYP2D1 (IC(50) , 20.89 mug/ml; K(i) , 9.34 mug/ml), CYP2C6/11 (IC(50) for diclofenac and S-mephenytoin, 56.98 and 31.59 mug/ml; K(i,) 39.0 and 23.8 mug/ml), and CYP2B1 (IC(50) , 48.49 mug/ml; K(i) , 36.3 mug/ml) in a noncompetitive manner. Induction study showed CSBTA had obvious inhibitory rather than inductive effects on CYP1A2 and CYP2C6/11. Interestingly, neither inhibition nor induction on CYP3A was observed for CSBTA. In conclusion, CSBTA-drug interactions might occur through CYP450s inhibition, particularly CYP1A and CYP2D. Further studies are still needed to elucidate the underlying mechanisms of inhibition.

Dehydrocavidine attenuates d-galactose induced learning and memory impairment in rats.[Pubmed:29208407]

Neurosci Lett. 2018 Feb 5;665:200-205.

OBJECTIVE: DehydroCavidine (DEH) is the major component of a plant corydalis saxicola Bunting, which is used to treat the patients with hepatic disorders, there is still no report about the effect of DEH on the brain disorder. In this study, the effect and mechanism of DEH on d-galactose (d-gala) induced learning and memory impairment in rats was investigated. METHODS: A learning and memory impairment rat model was employed by chronic intraperitoneal injection of d-gala and intragastric administration of DEH, then Morris water maze test was used to investigate the effect of DEH on learning and memory impairment, Golgi stain and biochemical methods, real time PCR were used to investigate underlying mechanism. RESULTS: Intraperitoneal injection of d-gala could induced severe learning and memory impairment in rats, intragastric administration of DEH could effectively attenuates these deficits. Golgi staining showed DEH supplementary could restored the density of spines to 5.7+/-1.16 spines per 10mum in the DEH+d-gala group (p<0.05). DEH supplementary administration reversed the lipid peroxides and restored the enzymes activities to reduce oxidative damage (p<0.05). DEH supplementary administration could reduced the production of NO and PGE2 and the mRNA expression of iNOS and COX-2 (p<0.05). CONCLUSIONS: DEH could attenuates d-gala induced learning and memory impairment in rats by enhancing synaptic plasticity, reducing oxidative damage and limiting the neuroinflammation.

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via NF-kappaB Signaling Pathway in vivo and in vitro.[Pubmed:28365871]

Inflammation. 2017 Aug;40(4):1111-1122.

Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of Cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with Cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of Cavidine to lung injury. The results showed that pretreatment with Cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-alpha and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that Cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-kappaB) p65 and IkappaBalpha induced by LPS. In conclusion, our results demonstrate that Cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-alpha and IL-6 production and NF-kappaB signaling pathway activation. Taken together, Cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.

Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer in mice and possible underlying mechanism.[Pubmed:27380619]

Int Immunopharmacol. 2016 Sep;38:450-9.

Cavidine, a major alkaloid compound isolated from Corydalis impatiens, has various pharmacological effects but its effect on gastric ulcer has not been previously explored. The current study aimed to investigate the possible anti-ulcerogenic potential of Cavidine in the model of ethanol-induced gastric ulcer. Mice received Cavidine (1, 5 or 10mg/kg, ig), cimetidine (CMD, 100mg/kg, ig) or vehicle at 12h and 1h before absolute ethanol administration (0.5mL/100g), and animals were euthanized 3h after ethanol ingestion. Gross and histological gastric lesions, biochemical, immunological and Western blot parameters were taken into consideration. The results showed that ethanol administration produced apparent mucosal injuries with morphological and histological damage, whereas Cavidine pre-treatment reduced the gastric injuries. Cavidine pre-treatment also ameliorated the contents of malonaldehyde (MDA) and myeloperoxidase (MPO) activity, and increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and prostaglandin E2 (PGE2), relative to the model group. Also Cavidine was able to decrease the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), inhibit the up-regulation of cyclo-oxygenase-2 (COX-2) expression and activation of Nuclear factor-kappa B (NF-kappaB) pathway. Taken together, these results indicated that Cavidine exerts a gastroprotective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, reduction of oxidative stress, suppression of NF-kappaB expression and subsequent reduced COX-2 and pro-inflammatory cytokines.

Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock.[Pubmed:27260672]

Toxicol Appl Pharmacol. 2016 Aug 15;305:46-54.

LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of Cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with Cavidine (1, 3 and 10mg/kg) or DEX (5mg/kg) at 1 and 12h before injecting LPS (30mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with Cavidine reduced the mortality of mice during 72h after endotoxin injection. In addition, Cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, Cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-alpha, IL-6 and HMGB1. Moreover, Cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, Cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-alpha, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway.

Protective effect of cavidine on acetic acid-induced murine colitis via regulating antioxidant, cytokine profile and NF-kappaB signal transduction pathways.[Pubmed:26102009]

Chem Biol Interact. 2015 Sep 5;239:34-45.

Ulcerative colitis is an inflammatory disorder characterized by neutrophils infiltration, oxidative stress, upregulation of pro-inflammatory mediators and cytokines. Cavidine possesses anti-inflammatory activity and has been used to treat various inflammatory diseases but its effect on ulcerative colitis has not been previously explored. The present study aims to evaluate the effect of Cavidine on acetic acid-induced ulcerative colitis in mice. Colitis mice induced by intra-rectal acetic acid (5%, v/v) administration received Cavidine (1, 5 and 10mg/kg, i.g) or sulfasalazine (500mg/kg, i.g) for seven consecutive days. After euthanized by cervical dislocation, colonic segments of mice were excised for clinical, macroscopic, biochemical and histopathological examinations. Results suggested treatment with Cavidine significantly decreased mortality rate, body weight loss, disease activity index (DAI), wet colon weight, macroscopic and histological score when compared with that of acetic acid-induced controls. In addition, administration of Cavidine effectively modulated expressions of MPO, GSH, SOD and MDA. Furthermore Cavidine inhibited the level of TNF-alpha and IL-6 in the serum and colon tissue in response to the regulation of p65 NF-kappaB protein expression. All these results indicated Cavidine exerts marked protective effect in experimental colitis, possibly by regulating the expression of oxygen metabolites, NF-kappaB and subsequent pro-inflammatory cytokines production.

Anti-inflammatory effects of cavidine in vitro and in vivo, a selective COX-2 inhibitor in LPS-induced peritoneal macrophages of mouse.[Pubmed:25373916]

Inflammation. 2015 Apr;38(2):923-33.

Cavidine is an isoquinoline alkaloid which is isolated from Corydalis impatiens. In traditional Tibetan herb, C. impatiens has been widely used for treatment of skin injuries, hepatitis, cholecystitis, and scabies. The present study aimed to evaluate its anti-inflammatory effect and investigate the mechanisms underlying this anti-inflammatory action. We used different inflammation model animals and lipopolysaccharide (LPS)-induced murine peritoneal macrophages to examine the anti-inflammatory function of Cavidine. Results indicated pretreatment with Cavidine (i.p.) decreased xylene-induced ear edema, formaldehyde-induced paw edema, leukocyte number, and the level of nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) in acetic acid-induced peritonitis in mice. The data also demonstrated that Cavidine significantly inhibited LPS-induced TNF-alpha, interleukin-6 (IL-6), and NO production in peritoneal macrophages. Moreover, Cavidine regulated the expression of cyclooxygenase-2 (COX-2) instead of cyclooxygenase-1 (COX-1) at protein levels. These results suggested that Cavidine is a selective COX-2 inhibitor which possesses an anti-inflammatory activity.

Simultaneous quantification of 11 isoquinoline alkaloids in Corydalis impatiens (Pall.) Fisch by HPLC.[Pubmed:23610009]

J Sep Sci. 2013 Jul;36(13):2090-5.

Isoquinoline alkaloids are the primary active ingredients of Corydalis, but an analytical method for quality assessment of the active ingredients in Corydalis impatiens (Pall). Fisch has not been reported. A new, simple, and multiple-component quantification method was developed for the simultaneous quantification of 11 isoquinoline alkaloids including capnoidine, chelianthifoline, bicuculline, protopine, isoapoCavidine, apoCavidine, Cavidine, tetrahydroepiberberine, ochotensimine, tetrahydrocoptisine, and tetrahydrocorysamine in C. impatiens. Separation of the isoquinoline alkaloids was performed on a RP C18 column (150 x 4.6 mm, 5 mum) with potassium dihydrogen phosphate buffer (pH 2.5, adjusted by phosphoric acid)/acetonitrile (53:47, v/v) containing 0.3% sodium dodecyl sulfonate. The flow rate and detection wavelength were set at 1 mL/min and 295 nm, respectively. Full validation of the assay was carried out including linearity, precision, accuracy, stability, LOD, and limit of quantitation. All calibration curves showed a good linear relationship (r > 0.999) in test range. The results demonstrated that the developed method was reliable, rapid, and specific. Six batches of C. impatiens samples from different sources were determined using the established method. The contents of alkaloids ranged from 11.68 to 351.83 mug/g. This method can be applied for quality evaluation and control of C. impatiens. Eleven isoquinoline alkaloids were first reported on simultaneous determination with HPLC.

Hepatoprotective effects and mechanisms of dehydrocavidine in rats with carbon tetrachloride-induced hepatic fibrosis.[Pubmed:21893185]

J Ethnopharmacol. 2011 Oct 31;138(1):76-84.

AIM OF THE STUDY: The current study was designed to examine the effects and possible mechanisms of dehydroCavidine (DC) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in male Sprague-Dawley (SD) rats. MATERIALS AND METHODS: Hepatic fibrosis was induced in male rats with CCl4 administration for 12 weeks. Liver histopathological study was performed, and the liver function was examined by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total bilirubin (TBIL) for evaluating the effect of DC on hepatic fibrosis. The possible mechanisms were investigated by measuring hepatic collagen metabolism and oxidative stress level. Furthermore, oligo microarray analysis of 263 genes was performed, and quantitative real-time RT-PCR was used to verify 4 of the abnormally expressed genes (Bcl2, Cyp3a13, IL18 and Rad50). RESULTS: DC treatment significantly inhibited the loss of body weight and the increase of liver weight induced by CCl4. DC also improved the liver function of rats as indicated by decreased serum enzymatic activities of ALT, AST, ALP and TBIL. Histopathological results indicated that DC alleviated liver damage and reduced the formation of fibrous septa. Moreover, DC significantly decreased liver hydroxyproline (Hyp) and increased urine Hyp. It also decreased liver malondialdehyde concentration, increased activities of liver superoxide dismutase, catalase and glutathione peroxidase. Microarray analysis revealed that DC altered the expression of genes related to apoptosis, cytokines and other proteins involved in tissue repair. CONCLUSIONS: Our findings indicate that DC can protect rats from CCl4-induced hepatic fibrosis through reducing oxidative stress, promoting collagenolysis, and regulating fibrosis-related genes.