Herbal Compound Research Articles

Therapeutic activities and biological effects of curcumin, as a natural multi-target compound, on human health: A minireview

Background and aims: Curcumin or diferuloylmethane is derived from ferulic acid. This herbal compound has a particular chemical structure and various biological/medical properties. The functional groups in the curcumin structure and its analogs are involved in the formation of specific biological activities. This natural compound has high bioactivity, as well as the potential to treat diseases such as cancer, Alzheimer’s, diabetes, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Considering the spread of infectious diseases and cancers in recent years, as well as an increase in drug resistance and side effects, providing effective and available treatments is necessary. Methods: This review explained the chemical structure of curcumin and covered its biological properties, including anti-inflammation, antioxidant, anti-cancer, neuroprotective, anti-diabetic, and anti-SARS-CoV-2 activities. Scientific databases were studied to gather the required information. Results: Curcumin affected several molecular pathways, including activating transcription factors, cell growth factors, anti-inflammatory agents, protein kinases, cytokines, and apoptotic pathway factors. Thus, it had beneficial therapeutic effects on health. Conclusion: By targeting a wide range of molecular mechanisms, curcumin has the potential to treat various diseases. Knowledge of curcumin’s pharmacological/biological activities and its action mechanisms can enhance the applications of curcumin as a potentially bioactive and therapeutic compound.

Study on the Effects of Kuanxiong Aerosol on the Isolated Artery and Rabbits Acute Myocardial Ischemia Model.

Kuan Xiong aerosol (KXA) is a Chinese herbal compound used to regulate qi-flowing to relieve pain and improve angina. However, only a few pharmacological studies on this traditional Chinese medicine preparation have been reported to confirm these activities. This article aims to observe the effect of resisting acute myocardial ischemia (AMI) in vivo and dilating vessel in vitro of KXA. The AMI model involves intravenously injecting the pituitary (2 U.kg-1) into the ear of rabbits. Electrocardiograph (ECG) T waves were then recorded after administration, and the falling range was calculated. Following this, the level of serum Cardiac troponin T (cTn-T) and the histopathology of the cardiac muscle tissue were evaluated. In vitro, the effect of KXA on vasodilation of isolated aortic rings that had been pre-contracted with KCl (30 mM) was observed. It was found that KXA reduced ECG ST-T waves and serum cTn-T in the rabbit AMI model, protecting myocardial tissue from fracturing and loss of myocardial fibers and inhibiting inflammatory cell infiltration, cavitation degeneration, and karyopyknosis of the myocardial matrix. Furthermore, the administration of 0.215, 1.075, and 2.150 mg.mL-1 of KXA resulted in significant relaxation of the aortic rings at a rate of 69.63 %, 90.14 %, and 118.72 % (p < 0.01) in the untreated ones, and a second shrinkage ratio of 20.17 %, 4.29 %, and 4.54 % (p < 0.01) in the untreated ones, respectively. These results suggest that KXA protects against AMI, contributes to the dilation of blood vessels, and has long-acting effectiveness.

Therapeutic Efficacy of Great Plantain (Plantago major L.) in the Treatment of Second-Degree Burn Wounds: A Case-Control Study.

Background Great plantain (Plantago major L. or P.major) is a medicinal plant that is available all around the world. The whole plant has several bioactive compounds including terpenoids, flavonoids, phenolic compounds, alkaloids, fatty acids, iridoid glycosides, polysaccharides, and vitamins. Scientific studies have recognized several medical benefits like wound healing, anti-inflammatory, antimicrobial, antiulcerative, and antioxidative agents. The wound-healing capacity of this plant has been investigated under in vivo and ex vivo conditions. In the current study, we aim to compare the therapeutic effect of the P.major extract with 1% sulfadiazine on the healing of second-degree burn wounds. Method Second-degree burn victims were included in our study. The investigation and control group, respectively, received P. major ointment 10% and silver sulfadiazine ointment 1%. The bacterial culture from the wound site was taken on days 3, 7, 10, 13, and last day of hospitalization. Patients' subjective complaints were obtained through the visual analog scale (VAS). All patients were treated and evaluated in the hospital. Result Among the 15 patients, 11 were male, and the mean age was 33.3 years. The average complete healing duration was 11.73 vs. 13 days in the P. major and control group, respectively (P=0.166). On the third day, infection control was similar between the two groups, and on the seventh day, all bacterial cultures were negative. Although there was a significant reduction in pain scores during the recovery time, no significant differences in pain reduction were noted between the two groups (P=0.849). Conclusion We showed that P.major ointment is a safe and suitable herbal compound in the treatment of second-degree burn wounds that not only has wound-healing properties but also is an analgesic and antimicrobial compound.

Protective effects of Herbal Compound (IM253) on the inflammatory responses and oxidative stress in a mouse model of multiple sclerosis

Multiple sclerosis (MS) is a multifactorial chronic inflammatory demyelinating disease of the central nervous system with both immune and neurodegenerative components as the underlying causes. Cytokines are key components of the inflammatory processes and their crucial roles in the inflammatory aspect of MS are undeniable. Several studies have pointed to the apparent change in Cytokines in MS. The aim of this study was to investigate the effects of IM253 treatment on inflammation and antioxidant defense in the cerebral corpus callosum of the C57BL/6 mouse, an Experimental autoimmune encephalomyelitis (EAE) model and as a most commonly used experimental model of MS. During the course of study, clinical evaluation was performed and eventually histological and molecular analysis on brain samples was carried out. Gene expression analyses demonstrated that treatment with IM253 causes a significant reduction in the expression of pro-inflammatory cytokine coding genes including IL-6, TNF-α, IFN-γ, and IL-17 as well as a significant increase in the expression of anti-inflammatory and anti-oxidant enzyme coding genes including TGF-β, GPX-1, and Cat. Histological studies also show that treatment with IM253 can reduce demyelination and inflammation (p<0.001). In addition, the GPX-1 enzyme activity evaluation also demonstrated that total antioxidant capacity was significantly higher in IM253 treated mice (p<0.001). Overall, our results suggest that IM253 could ameliorate the severity of EAE, probably because of its anti-inflammatory and anti-oxidant properties, and support the preclinical effects of IM253 as a potential therapeutic intervention.

Hesperetin promotes longevity and delays aging via activation of Cisd2 in naturally aged mice

BackgroundThe human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an effective way of delaying aging.MethodsHesperetin was identified as a promising Cisd2 activator by herb compound library screening. Hesperetin has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used to investigate the effect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural defects and functional decline. Tissue-specific Cisd2 knockout mice were used to study the Cisd2-dependent anti-aging effects of hesperetin. RNA sequencing was used to explore the biological effects of hesperetin on aging.ResultsThree discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregulation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during old age.ConclusionsOur findings indicate that a Cisd2 activator, hesperetin, represents a promising and broadly effective translational approach to slowing down aging and promoting longevity via the activation of Cisd2.

Farrerol exhibits inhibitory effects on lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway.

Farrerol is an herbal compound extracted from rhododendron. Here, our study is to investigate biological effects of farrerol on lung adenocarcinoma (LAC) cells. Human LAC cell lines and xenograft mouse model were utilized to define the effects of farrerol on tumor growth. Our findings indicated that farrerol significantly reduced LAC cell viability as well as the colony-forming capacity. Flow cytometry analysis demonstrated that farrerol contributed to cell apoptosis and G0/G1 phase cell cycle arrest. Mechanistically, farrerol treatment upregulated proapoptotic molecules (Bak, Bid, cleaved caspase-3 and cleaved caspase-9) and senescence markers (p16 and p2), but downregulated antiapoptosis genes (Bcl-2 and Bcl-XL) and cell cycle-associated genes (CyclinD1 and CDK4); meanwhile, the phosphorylation of retinoblastoma (Rb) protein was attenuated upon pretreatment of LAC cells with farrerol in comparison to untreated control. Further studies indicated that farrerol elevated reactive oxygen species levels, activating mitochondrial apoptotic pathway and causing cell apoptosis. However, exposure to farrerol did not result in significant apoptosis in normal lung epithelial cells, suggesting a tumor-specific effect of farrerol on LAC cells. In animal model, farrerol showed a significant inhibitory effect on LAC xenograft tumor growth. And gene expressions in tumor tissues, as mentioned above, were in line with the in vitro results. Taken together, these results suggested that farrerol caused LAC cell apoptosis by activating mitochondrial apoptotic pathway, whereas farrerol treatment had no notable effect on normal lung epithelial cells. Farrerol might be an effective therapeutic drug for LAC.

Pharmaceutico analytical study of Guduchyadi Avaleha - Modified form of Guduchyadi Ghrita

Introduction- Stuttering (Gadgada) word itself indicates the disease in which fluency of speech is impaired. It denotes the un-cleared speech (Avyakta Vak or Shabdha). In Vangsen Samhita, the group of 8 drugs with honey is cited for the treatment of stuttering entitled as Guduchyadi Ghrita. Palatability of Guduchyadi Ghrita is the major concern in the treatment of children to administer as most of children unlike it, so by keeping this in mind Avaleha formulation is prepared which is easily administrable. Guduchyadi Avaleha is a herbo-mineral confection which is prepared by using sugar as a base. This herbal compound is formulated by experienced Aacharya of Ayurved and is used in practice for stuttering. Though it’s a potent formulation; but no standardized reports are available for the manufacturing process of the Guduchyadi Avaleha or its preliminary physico-chemical profiles. Therefore, manufacturing standardize process of preparation and preliminary physic-chemical profiles of Guduchyadi leha was planned. Methods- The prepared lickable formulation was lay open for the analysis of pharmacognostical and pharmaceutical properties like as pH value, Microscopic analysis, loss on drying the sample, reading of ash value, etc. Results – After analysis of Pharmacognostical organoleptic study, loss on drying value, pH, Ash value, Water soluble extract, the result was shown. Conclusion –All the characteristic of formulation sample was observed and the result can be taken as standard value for guduchyadi avaleha.

Capsaicin Inhibits Shigella flexneri Intracellular Growth by Inducing Autophagy.

Antibiotic treatment plays an essential role in preventing Shigella infection. However, incidences of global rise in antibiotic resistance create a major challenge to treat bacterial infection. In this context, there is an urgent need for newer approaches to reduce S. flexneri burden. This study largely focuses on the role of the herbal compound capsaicin (Caps) in inhibiting S. flexneri growth and evaluating the molecular mechanism behind bacterial clearance. Here, we show for the first time that Caps inhibits intracellular S. flexneri growth by inducing autophagy. Activation of autophagy by Caps is mediated through transcription factor TFEB, a master regulator of autophagosome biogenesis. Caps induced the nuclear localization of TFEB. Activation of TFEB further induces the gene transcription of autophagosomal genes. Our findings revealed that the inhibition of autophagy by silencing TFEB and Atg5 induces bacterial growth. Hence, Caps-induced autophagy is one of the key factors responsible for bacterial clearance. Moreover, Caps restricted the intracellular proliferation of S. flexneri-resistant strain. The efficacy of Caps in reducing S. flexneri growth was confirmed by an animal model. This study showed for the first time that S. flexneri infection can be inhibited by inducing autophagy. Overall observations suggest that Caps activates TFEB to induce autophagy and thereby combat S. flexneri infection.

Efficacy and Safety of Shenqisuxin Granule for Non-ST-segment Elevation Acute Coronary Syndrome: Study Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial.

IntroductionThe Chinese herbal compound formula, Shenqisuxin granule (SQSX), promotes neovascularization and prevents in-stent restenosis in modern pharmaceutical studies and is expected to provide an effective strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS). Thus, this study aims to examine the efficacy and safety of SQSX for NSTEACS and initially reveal its mechanism.Methods/DesignThe study is a randomized, double-blinded and placebo-controlled trial. A total of 66 participants will be randomly allocated to one of the following two groups. Participants in the SQSX group will receive conventional treatment plus SQSX, while the placebo group will receive conventional treatment plus placebo, both for 14 days. The primary outcome, hs-CRP, and secondary outcome the Seattle Angina Questionnaire (SAQ) will be assessed at baseline, 7 ± 3 days and 14 ± 3 days. At all visit windows, other indicators including creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponins I (cTnI), 12-lead electrocardiograph and the syndrome scores of Qi deficiency and blood stasis will be tested and metagenomic sequencing for intestinal flora will be performed. Echocardiography and safety assessment will be performed at baseline and 14 ± 3 days. Adverse events will be monitored during the trial.DiscussionThe purpose of the study is to examine the efficacy and safety of SQSX to improve NSTEACS and initially reveal its mechanism.Trial RegistrationChina Clinical Trial Registry, ChiCTR2000029226. Registered on January 19, 2020.

Novel bi-layered dressing patches constructed with radially-oriented nanofibrous pattern and herbal compound-loaded hydrogel for accelerated diabetic wound healing

The clinical treatment of chronic wounds caused by different pathophysiological ulcers like diabetic ulcers still remains a bottleneck. Although numerous approaches have been designed and developed, their therapeutic effects cannot meet the medical needs due to the complicated pathological microenvironment and restricted regenerative capacity of hard-healing chronic wounds. In this study, novel bi-layered and multifunctional dressing patches constructed with one layer of electrospun methacrylated gelatin (MeGel)/poly (L-lactic acid) (PLLA) radially-oriented nanofiber mats (RNMs) and one layer of Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SRHC)-loaded MeGel hydrogel were designed to promote the closure and healing of diabetic wounds. An innovative electrospinning method was firstly designed and implemented to generate MeGel/PLLA RNMs, which were demonstrated to be a more appropriate nanofiber pattern for effectively guiding migration and promoting proliferation of human dermal fibroblasts (HDFs) compared with the conventional electrospun MeGel/PLLA haphazardly-oriented nanofiber mats (HNMs) and MeGel/PLLA uniaxially-oriented nanofiber mats (UNMs). Importantly, the in vivo mice acute full-thickness defect models also confirmed that MeGel/PLLA RNMs could significantly promote the cell migration and accelerate the healing rate throughout providing the cell recruitment and regulation abilities in comparison with MeGel/PLLA HNMs and UNMs. The MeGel hydrogel precursors loaded with different concentrations of SRHC were employed to generate the hydrogel layers on the MeGel/PLLA RNMs, and therefore a series of bi-layered wound dressing patches with integrated multifunctional properties were fabricated. All the bi-layered wound dressing patches with or without SRHC showed excellent hemostatic performances. The bi-layered dressing patches containing SRHC exhibited great antibacterial property to both E. coli and S. aureus, and also high cell survival rate to HDFs. For the in vivo full-thickness diabetic wound healing test, the bi-layered dressing patches without SRHC exhibited a faster wound healing rate compared with the medical gauzes. Furthermore, the 10% SRHC loaded bi-layered dressing patches significantly accelerated the high-quality regeneration and healing of diabetic wounds by effectively reducing the inflammation, promoting the vascularization, and facilitating the regeneration of hair follicles. Specifically, the 10% SRHC loaded bi-layered dressing patches presented a high healing area of 97.4 ± 2.8% at day 18 after surgery. Our present study demonstrated that the SRHC contained bi-layered dressing patches show great potential for the treatment of hard-healing diabetic wounds.

Efficacy of a Persian herbal medicine compound on coronavirus disease 2019 (COVID-19): A randomized controlled trial

BackgroundThe global attention to the capacities of traditional medicine for alleviating the clinical manifestations of COVID-19 has been growing. The present trial aimed to evaluate the efficacy and safety of a Persian herbal medicine formula among patients with COVID-19. MethodsThe present trial was conducted in Afzalipour hospital, Kerman, Iran, from June to September 2020. Hospitalized COVID-19 patients were randomly divided into intervention (Persian herbal medicine formula + routine treatment) or control (only routine treatment) groups. The intervention group received both capsule number 1 and 2 every 8 hours for 7 days. Capsule number 1 contained extract of the Glycyrrhiza glabra, Punica granatum, and Rheum palmatum, and the second capsule was filled by Nigella sativa powder. Participants were followed up to 7 days. The primary outcome was the number of hospitalization days, while cough, fever, and respiratory rate, days on oxygen (O2) therapy, and mortality rate were considered as the secondary outcomes. ResultsEighty-two patients were enrolled to the study, while 79 cases completed the trial and their data were analyzed (mean age: 59.1 ± 17.1 years). Based on the results, the Persian medicine formula decreased the mean hospitalization days, so that the mean difference of length of hospitalization as primary outcome was 2.95 ± 0.43 days. A significant clinical improvement was observed regarding dyspnea, need for O2) therapy, and respiratory rate in the intervention group. No adverse effects were reported. ConclusionThe present study supported the use of the Persian medicine formula as an adjuvant therapy for hospitalized COVID-19 patients. Study registrationIranian Registry of Clinical Trials (www.irct.ir): IRCT20200330046899N1.

Qualitative and quantitative analysis of multi-components in Xing-Su-Ning Capsules for quality improvement

Xin-Su-Ning Capsules (XSNC) is an effective prescription for the treatment of arrhythmia composed of eleven Chinese herbs. With the wide application of XSNC in clinic, its quality control issues have also received increasing attention. Based on the multi-components characteristics of Chinese herbal compound, there is an urgent need to establish a quality evaluation system. Gas chromatography-mass spectrometry (GC-MS) and ultra high-performance liquid chromatography quadrupole electrostatic orbitrap high resolution mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) were performed to identify the preliminary chemical profile of XSNC. Subsequently, a rapid ultra high-performance liquid chromatography coupled with electrospray ionization triple-quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was developed to evaluate the quality of XSNC through a simultaneous determination of 16 components. A total of 21 volatile components and 59 non-volatile compounds were tentatively identified from the XSNC, each identified compound is marked on the corresponding chromatogram. Moreover, sixteen chemical constituents (sophocarpine, matrine, febrifugine, berberine, palmatine, Tangeratin, nobiletin, liensinine, neferine, scopoletin, isoliquiritigenin, liquiritigenin, naringenin, naringin, hesperidin and glycyrrhizic acid) were quantified by the developed UHPLC-QQQ-MS/MS method. The method validation of the sixteen compounds was performed with acceptable linearity (R 2 , 0.9990-1.0000), precision (RSD, 0.25-2.06%), repeatability (RSD, 0.93-2.90%) and recovery (99.65%-104.03%, RSD≤4.35%). This qualitative analysis method sensitive and reliable for searching the volatile and non-volatile compounds from XSNC. The linearity, accuracy and precision of the quantitative analysis method were satisfactory. It is proposed that the methods described here can be applied for rapid evaluation, quality control and authenticity establishment of XSNC.

Effect of Traditional Chinese Medicine on Allergic Rhinitis in Children under Data Mining.

The data mining analysis of the medication rule and the curative effect of traditional Chinese medicine in treating allergic rhinitis in children was performed by using the association rule Apriori algorithm. The model of interest degree was introduced to improve the Apriori algorithm, and the performance difference of the algorithm before and after improvement was analyzed. Traditional Chinese medicine prescriptions for the treatment of allergic rhinitis in children were selected from the dictionary of Chinese medicine formulations. The frequency, frequent itemsets, and the improved Apriori algorithm of each prescription were analyzed comprehensively. The results showed that both the execution time of the improved Apriori algorithm and the number of mining association rules were signally lower. 102 Chinese herbal compounds were selected, in which the occurrence frequency of Flos magnoliae was the highest (67 times, 5.33%). The occurrence frequency of diaphoretic drugs was the highest (412 times, 32.78%) in drug types. The occurrence frequency of Yu Ping Feng powder was the highest (21 times, 20.59%) in the Chinese herbal compound. After the association rule analysis of the improved Apriori algorithm, Perilla frutescens, Saposhnikovia divaricata, ginseng, Notopterygium root, and Astragalus propinquus Schischkin were often mixed with liquorice, and Flos magnoliae were usually mixed with Fructus xanthii and black plum. Compared with the conditions before treatment, the sign scores of children with allergic rhinitis were remarkably decreased after treatment with traditional Chinese medicine compounds (P < 0.05). The mining performance of the Apriori algorithm was improved by introducing an interest-based model. The treatment of traditional Chinese medicine on allergic rhinitis in children was combined with children's physiological and pathological characteristics of children, which used mild medicines.

Identification of the Active Compound of Liu Wei Di Huang Wan for Treatment of Gestational Diabetes Mellitus via Network Pharmacology and Molecular Docking.

Liu Wei Di Huang Wan (LWDHW) is a well-known Chinese herbal compound, which has been prescribed for the treatment of gestational diabetes mellitus (GDM). We sought to clarify the potential therapeutic effects of LWDHW against GDM. Differentially expressed genes (DEGs) in GDM were firstly identified from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the biological functions of the DEGs. Subsequently, the LWDHW-compound–target network was constructed based on public databases to identify the relationship between the active components in LWDHW and the corresponding targets. Furthermore, gene functional analysis and protein–protein interaction (PPI) network construction were applied to investigate the function of potential targets and to evaluate hub genes. Finally, molecular docking was used to verify the binding activities between active ingredients and hub targets. Thirteen active components and 39 corresponding therapeutic target genes were obtained via network pharmacology analysis. The enrichment analysis demonstrated that the anti-GDM effect of LWDHW included oxidoreductase activity, involvement in renal system process, and regulation of blood pressure, which may be achieved through regulation of serotonergic synapses, vascular smooth muscle contraction, and neuroactive ligand–receptor interaction pathways. Additionally, molecular docking revealed that the main active component, Mu Dan Pi, exhibited the best affinity for proteins encoded by hub genes. This study applied network pharmacology analysis and molecular docking to display the multicomponent and multitarget characteristics of LWDHW in the treatment of GDM. Our findings provide novel insights into the pathogenesis of GDM and the therapeutic mechanisms of LWDHW against GDM.

Research progress in mechanism of Chinese herbal compounds and monomers in delaying lumbar intervertebral disc degeneration

Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/β-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.

Interaction of compounds derived from the Chinese medicinal formula Huangqi Guizhi Wuwu Tang with stroke-related numbness and weakness targets: An in-silico docking and molecular dynamics study

Huangqi Guizhi Wuwu Tang (HGWT) is a traditional Chinese herbal formula used for managing post-stroke symptoms. Existing research have supported the use of this formula particularly for stroke-related numbness and weakness (SRNW); however, their mechanisms of actions are not fully understood. This study aims to investigate the molecular mechanisms of components from HGWT targeting specific proteins related to numbness and weakness through computational docking and molecular dynamics (MD) simulations. A total of 786 compounds from HGWT were retrieved from a herbal compound database and docked against a candidate SRNW target protein, with the asernestioside B (HQ068)-mitogen-activated protein kinase 3 (MAPK3) complex predicted to exhibit the highest binding affinity (−10.4 kcal/mol) and number of ligand-receptor contacts. Subsequent molecular dynamics (MD) simulations were performed in triplicate on the apo-MAPK3 protein and asernestioside B -bound form in a solvated system for 200 ns per trajectory to ascertain the stability of the enzyme-ligand complex, and to determine the structural impact of ligand binding. The stability of the complex and overall tertiary structural changes were characterized using root-mean-square deviation (RMSD), radius of gyration (Rg), root-mean-square fluctuation (RMSF) calculations Differences in the RMSF of apo and ligand-bound MAPK3 were most prominent in three major regions: (a) activation loop Asp184:Pro213 (b) MAPK3 insertion site Gly262:Ala291 and (c) loop region at the C-terminus Tyr334:Pro356. Lower values of RMSF for the HQ068-bound protein at the activation loop suggest that HQ068 binding stabilizes MAPK3 in a different conformation in this region compared to the apo protein. Free energy calculations of the asernestioside B-MAPK3 complex revealed key residues contributing to the interaction, which include Pro264, Gln 266, Asp268 and Thr288. These key residues may play an integral role in the binding of selective modulators or substrates of extracellular signal-regulated kinase (ERK) within the MAPK cascade. Overall, this study provides a mechanistic overview of compounds from HGWT. Modelling predicted that asernestioside B may act with high potency against MAPK3, while exhibiting a favourable ADMET profile, and this compound should be explored as a potential agent to alleviate SRNW-related symptoms in future studies.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61

ObjectivePsoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. MethodsThe expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. ResultsImmunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. ConclusionThe results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Study on the antifungal mechanism of Chinese herbal extract on Botryosphaeria dothidea

Botryosphaeria dothidea is a main post-harvest pathogen of kiwifruit, causing fruit decay and health problems. In this study, the effect of Chinese herbal extract compound (CHEC) on the antifungal assay, the SEM (scanning electron microscope) observation, fluorescence microscopy observation, transcriptional profile, and physiological characters of B. dothidea was measured. CHEC (0.6 to 0.8 mg/ml) significantly inhibited mycelium growth, reduced the formation and germination of spores, and decreased the content of sugar and protein in the mycelium. The activity of SOD, CAT, POD, NADP-malate dehydrogenase, succinate dehydrogenase, cellulase, and glucanase was significantly reduced, while the content of malondialdehyde in the mycelium was significantly increased. In addition, there was a significant decrease in DNA content and mitochondrial membrane potential and a significant increase in ROS. The mycelium appeared thicker, the top of the mycelium was significantly larger, the cell membrane of spores began to contract and bend, and the nucleus gradually disappeared. Transcriptome data showed that a total of 20,510 differentially expressed genes (DEGs) were obtained, including 19,139 down-regulated and 1371 up-regulated genes. Both RNA-seq data and qRT-PCR showed that the genes of remarkable down-regulation were included in the membrane pathway, cell pathway, oxidoreductase activity pathway, transport and catabolism, and carbohydrate metabolism. Practical applications CHEC is a mixture of several extracts with strong antifungal effects. It is a green and safe antifungal agent. CHEC has a strong antifungal effect by destroying mycelial cell structure, inhibiting gene expression and mycelial growth and metabolism. These findings provided additional useful information on the antifungal mechanism of CHEC at the molecular and genetic levels, and suggested that CHEC was a potential candidate to control B. dothidea. Moreover, our data provided novel insights into the green and safe preservation of kiwifruit.

Atractylenolide III ameliorates spinal cord injury in rats by modulating microglial/macrophage polarization.

BackgroundInflammatory reactions induced by spinal cord injury (SCI) are essential for recovery after SCI. Atractylenolide III (ATL‐III) is a natural monomeric herbal bioactive compound that is mainly derived in Atractylodes macrocephala Koidz and has anti‐inflammatory and neuroprotective effects.ObjectiveHere, we speculated that ATL‐III may ameliorate SCI by modulating microglial/macrophage polarization. In the present research, we focused on investigating the role of ATL‐III on SCI in rats and explored the potential mechanism.MethodsThe protective and anti‐inflammatory effects of ATL‐III on neuronal cells were examined in a rat SCI model and lipopolysaccharide (LPS)‐stimulated BV2 microglial line. The spinal cord lesion area, myelin integrity, and surviving neurons were assessed by specific staining. Locomotor function was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale, grid walk test, and footprint test. The activation and polarization of microglia/macrophages were assessed by immunohistofluorescence and flow cytometry. The expression of corresponding inflammatory factors from M1/M2 and the activation of relevant signaling pathways were assessed by Western blotting.ResultsATL‐III effectively improved histological and functional recovery in SCI rats. Furthermore, ATL‐III promoted the transformation of M1 into M2 and attenuated the activation of microglia/macrophages, further suppressing the expression of corresponding inflammatory mediators. This effect may be partly mediated by inhibition of neuroinflammation through the NF‐κB, JNK MAPK, p38 MAPK, and Akt pathways.ConclusionThis study reveals a novel effect of ATL‐III in the regulation of microglial/macrophage polarization and provides initial evidence that ATL‐III has potential therapeutic benefits in SCI rats.

Genotoxic, antigenotoxic and protective evaluation of Musalyadi churna by chromosomal aberration assay in Swiss albino mice

Ayurveda is an ancient science of life that uses a wide range of formulations or herbal compounds to treat various diseases. Each drug must be scientifically, pre-clinically, and clinically evaluated in order to gain global acceptance. As part of the safety evaluation process, regulatory authorities around the world require data on new drug genotoxic potential.MusalyadiChurna(MSDC) is a classical Ayurvedic formulation in herbal powder dosage form consisting of eight ingredients of herbal origin and indicatedin the treatment infertility. This herbal combination may be useful, however mixture of substances can be dangerous and genotoxic, causing harm to living cells' genetic material and resulting in mutations that induce serious issues for the host, such as cancer and birth defects; consequently, genotoxicity testing is essential.The study aimed to evaluate the genotoxic, antigenotoxic and protective properties of MusalyadiChurnaagainst the bone marrow of albino mice. MusalyadiChurna's genotoxicity were assessed using the "Mammalian Bone Marrow Chromosome Aberration assay," and the classical powder's antigenotoxic and protective activities against cyclophosphamide-induced genotoxicity in mice were also assessed using the same assay.Mice were administered MusalyadiChurna orally for four weeks at a dose of 25 mg/25 g mouse. Cyclophosphamide was utilized as a mutagen, and a single dose of 50 mg/kg b.w. was given intraperitoneally (i.p.) 24 hours after the final dose of MusalyadiChurna in the pre-treatment regimen and 24 hours before the first dose of MusalyadiChurna in the post-treatment regimen.The chromosomal aberration assay revealed that the herbal compound formulation MusalyadiChurnaat 1000 mg/Kg body wt. had no genotoxic activity against the bone marrow of Swiss albino mice. Using the same experiment, the formulation demonstrated both protective and antigenotoxic properties against Cyclophosphamide-induced mutagenicity in mice.Further research should be to capitalize on MusalyadiChurna’s potential as an alternative source of natural compounds to treat genotoxic problems.