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Keywords = traditional herbal formula

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15 pages, 1302 KiB  
Article
Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors
by Ching-Hsuan Liu, Yu-Ting Kuo, Chien-Ju Lin, Feng-Lin Yen, Shu-Jing Wu and Liang-Tzung Lin
Viruses 2025, 17(8), 1086; https://doi.org/10.3390/v17081086 - 5 Aug 2025
Abstract
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, [...] Read more.
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article
(This article belongs to the Section Coronaviruses)
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25 pages, 8335 KiB  
Article
Integrative In Silico and In Vivo Analysis of Banhasasim-Tang for Irritable Bowel Syndrome: Mechanistic Insights into Inflammation-Related Pathways
by Woo-Gyun Choi, Seok-Jae Ko, Jung-Ha Shim, Chang-Hwan Bae, Seungtae Kim, Jae-Woo Park and Byung-Joo Kim
Pharmaceuticals 2025, 18(8), 1123; https://doi.org/10.3390/ph18081123 - 27 Jul 2025
Viewed by 445
Abstract
Background/Objectives: Banhasasim-tang (BHSST) is a traditional herbal formula commonly used to treat gastrointestinal (GI) disorders and has been considered a potential therapeutic option for irritable bowel syndrome (IBS). This study aimed to explore the molecular targets and underlying mechanisms of BHSST in IBS [...] Read more.
Background/Objectives: Banhasasim-tang (BHSST) is a traditional herbal formula commonly used to treat gastrointestinal (GI) disorders and has been considered a potential therapeutic option for irritable bowel syndrome (IBS). This study aimed to explore the molecular targets and underlying mechanisms of BHSST in IBS using a combination of network pharmacology, molecular docking, molecular dynamics simulations, and in vivo validation. Methods: Active compounds in BHSST were screened based on drug-likeness and oral bioavailability. Potential targets were predicted using ChEMBL, and IBS-related targets were obtained from GeneCards and DisGeNET. A compound–target–disease network was constructed and analyzed via Gene Ontology and KEGG pathway enrichment. Compound–target interactions were further assessed using molecular docking and molecular dynamics simulations. The in vivo effects of eudesm-4(14)-en-11-ol, elemol, and BHSST were evaluated in a zymosan-induced IBS mouse model. Results: Twelve BHSST-related targets were associated with IBS, with enrichment analysis identifying TNF signaling and apoptosis as key pathways. In silico simulations suggested stable binding of eudesm-4(14)-en-11-ol to TNF-α and kanzonol T to PIK3CD, whereas elemol showed weak interaction with PRKCD. In vivo, eudesm-4(14)-en-11-ol improved colon length, weight, stool consistency, TNF-α levels, and pain-related behaviors—effects comparable to those of BHSST. Elemol, however, showed no therapeutic benefit. Conclusions: These findings provide preliminary mechanistic insight into the anti-inflammatory potential of BHSST in IBS. The integrated in silico and in vivo approaches support the contribution of specific components, such as eudesm-4(14)-en-11-ol, to its observed effects, warranting further investigation. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 2nd Edition)
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32 pages, 18091 KiB  
Article
Yinchenhao Decoction Mitigates Cholestatic Liver Injury in Mice via Gut Microbiota Regulation and Activation of FXR-FGF15 Pathway
by Weiwei Li, Doudou Huang, Zichen Luo, Ting Zhou and Ziwen Jin
Pharmaceuticals 2025, 18(7), 932; https://doi.org/10.3390/ph18070932 - 20 Jun 2025
Viewed by 594
Abstract
Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s [...] Read more.
Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD’s therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut–liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD’s efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases. Full article
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20 pages, 3284 KiB  
Article
Suk-SaiYasna Remedy, a Traditional Thai Medicine, Mitigates Stress-Induced Cognitive Impairment via Keap1-Nrf2 Pathway
by Wuttipong Masraksa, Supawadee Daodee, Orawan Monthakantirat, Chantana Boonyarat, Charinya Khamphukdee, Pakakrong Kwankhao, Abdulwaris Mading, Poowanarth Muenhong, Juthamart Maneenet, Suresh Awale, Kinzo Matsumoto and Yaowared Chulikhit
Int. J. Mol. Sci. 2025, 26(11), 5388; https://doi.org/10.3390/ijms26115388 - 4 Jun 2025
Viewed by 822
Abstract
Suk-SaiYasna (SSY) is a well-documented traditional Thai herbal formula in the Royal Scripture of King Narai’s Traditional Medicine. SSY contains Cannabis sativa leaves as a key ingredient and has traditionally been used to promote sleep, alleviate stress-related symptoms, and stimulate appetite. This study [...] Read more.
Suk-SaiYasna (SSY) is a well-documented traditional Thai herbal formula in the Royal Scripture of King Narai’s Traditional Medicine. SSY contains Cannabis sativa leaves as a key ingredient and has traditionally been used to promote sleep, alleviate stress-related symptoms, and stimulate appetite. This study aimed to investigate the neuroprotective effects of SSY in a mouse model of unpredictable chronic mild stress (UCMS)-induced cognitive impairment and explore the underlying mechanisms, particularly antioxidant enzyme pathways. Behavioral tests, including the Y-maze test, novel object recognition test, and Morris water maze test, demonstrated that UCMS-exposed mice exhibited cognitive impairment compared to non-stress mice. However, SSY treatment significantly improved learning and memory performance in UCMS-exposed mice. Mechanistic studies revealed that SSY reduced lipid peroxidation in the hippocampus and frontal cortex, key brain regions affected by chronic stress. Furthermore, UCMS significantly reduced the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), whereas SSY treatment restored their activity, indicating antioxidative and neuroprotective effects in vivo. Gene expression analysis further revealed that SSY regulates oxidative stress via the Nrf2/Keap1 signaling pathway. In vitro studies using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay confirmed the radical scavenging activities of SSY and its herbal components, demonstrating significant antioxidant potential. Phytochemical analysis identified delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinolic acid A, and cannabinoids as bioactive compounds in SSY, along with potent antioxidants such as gallic acid, myricetin, myristicin, piperine, costunolide, and gingerol. These findings suggest that the SSY formula mitigates UCMS-induced cognitive function through its antioxidant properties via multiple pathways, including radical scavenging activities, modulating the Nrf2-Keap1 pathway, inducing the expression of HO-1, NQO1 mRNAs, and other antioxidant enzymes. This work bridges traditional Thai medicine with modern neuropharmacology. Full article
(This article belongs to the Special Issue Natural Products for Neuroprotection and Neurodegeneration)
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29 pages, 4999 KiB  
Systematic Review
Integrating Acupuncture and Herbal Medicine into Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of East Asian Traditional Medicine
by Xiangping Peng, Bo Wu, Siyu Zhou, Yinghan Xu, Atsushi Ogihara, Shoji Nishimura, Qun Jin and Gerhard Litscher
Healthcare 2025, 13(11), 1326; https://doi.org/10.3390/healthcare13111326 - 3 Jun 2025
Cited by 2 | Viewed by 1400
Abstract
Background: Assisted reproductive technologies (ARTs) are essential in treating infertility but often face limited success due to low implantation and live birth rates. East Asian traditional medicine (EATM), including acupuncture and herbal medicine (HM), may enhance physiological responses during ART cycles. This study [...] Read more.
Background: Assisted reproductive technologies (ARTs) are essential in treating infertility but often face limited success due to low implantation and live birth rates. East Asian traditional medicine (EATM), including acupuncture and herbal medicine (HM), may enhance physiological responses during ART cycles. This study evaluated the effectiveness and safety of EATM in improving clinical pregnancy and live birth outcomes in women undergoing ART. Methods: This review, registered in PROSPERO (CRD42023411712), systematically searched 11 databases up to 31 March 2023. We included randomized controlled trials (RCTs) comparing EATM interventions to control groups. Data extraction and quality assessment were performed independently by two authors. Meta-analysis used the inverse-variance method in Stata 12.0. A total of 37 RCTs involving 10,776 women (aged 29–38) were analyzed. Studies addressed infertility causes including polycystic ovary syndrome, tubal blockage, diminished ovarian reserve, and unexplained infertility. Acupuncture therapies included body, electro-, laser, and auricular acupuncture. Herbal treatments were administered as powders, pills, granules, decoctions, and ointments based on traditional Chinese formulas. Results: EATM interventions were associated with significant improvements in clinical pregnancy and live birth rates. Acupuncture increased clinical pregnancy rates (CPR: RR 1.316, 95% CI 1.171–1.480) and live birth rates (LBR: RR 1.287, 95% CI 1.081–1.533). HM also enhanced CPRs (RR 1.184) and LBRs (RR 1.147). Subgroup analysis showed true acupuncture and HM were more effective than sham or placebo. No significant differences in adverse events were found. Conclusions: EATM, particularly acupuncture and HM, appears to be a safe and effective complementary therapy that can be used to improve ART outcomes. Future research should focus on developing standardized acupuncture and herbal protocols to optimize integration with ART. Full article
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27 pages, 5990 KiB  
Article
Neuroprotective Effects of Qi Jing Wan and Its Active Ingredient Diosgenin Against Cognitive Impairment in Plateau Hypoxia
by Tiantian Xia, Ziqiao Yan, Pan Shen, Mingyang Chang, Nan Zhang, Yunan Zhang, Qi Chen, Rui Wang, Li Tong, Wei Zhou, Zhexin Ni and Yue Gao
Pharmaceuticals 2025, 18(5), 738; https://doi.org/10.3390/ph18050738 - 17 May 2025
Viewed by 614
Abstract
Background/Objectives: High-altitude environments have a significant detrimental impact on the cognitive functions of the brain. Qi Jing Wan (QJW), a traditional herbal formula composed of Angelica sinensis, Astragalus membranaceus, and Rhizoma Polygonati Odorati, has demonstrated potential efficacy in treating [...] Read more.
Background/Objectives: High-altitude environments have a significant detrimental impact on the cognitive functions of the brain. Qi Jing Wan (QJW), a traditional herbal formula composed of Angelica sinensis, Astragalus membranaceus, and Rhizoma Polygonati Odorati, has demonstrated potential efficacy in treating cognitive disorders. However, its effects on cognitive dysfunction in plateau hypoxic environments remain unclear. Methods: In this study, acute and chronic plateau cognitive impairment mouse models were constructed to investigate the preventive and therapeutic effects of QJW and its significant active ingredient, diosgenin (Dio). Behavioral experiments were conducted to assess learning and memory in mice. Morphological changes in hippocampal neurons and synapses were assessed, and microglial activation and inflammatory factor levels were measured to evaluate brain damage. Potential active ingredients capable of crossing the blood–brain barrier were identified through chemical composition analysis and network database screening, followed by validation in animal and brain organoid experiments. Transcriptomics analysis, immunofluorescence staining, and molecular docking techniques were employed to explore the underlying mechanisms. Results: QJW significantly enhanced learning and memory abilities in plateau model mice, reduced structural damage to hippocampal neurons, restored NeuN expression, inhibited inflammatory factor levels and microglial activation, and improved hippocampal synaptic damage. Transcriptomics analysis revealed that Dio alleviated hypoxic brain damage and protected cognitive function by regulating the expression of PDE4C. Conclusions: These findings indicate that QJW and its significant active ingredient Dio effectively mitigate hypoxic brain injury and prevent cognitive impairment in high-altitude environments. Full article
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61 pages, 5997 KiB  
Review
A Direct Relationship Between ‘Blood Stasis’ and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment
by Douglas B. Kell, Etheresia Pretorius and Huihui Zhao
Pharmaceuticals 2025, 18(5), 712; https://doi.org/10.3390/ph18050712 - 12 May 2025
Cited by 2 | Viewed by 3399
Abstract
‘Blood stasis’ (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (血瘀). Similar concepts exist in Traditional Korean Medicine (‘Eohyul’) and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large [...] Read more.
‘Blood stasis’ (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (血瘀). Similar concepts exist in Traditional Korean Medicine (‘Eohyul’) and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down (‘stasis’) of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke. Full article
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15 pages, 2033 KiB  
Article
Skin Anti-Aging Properties of the Glycopeptide- and Glycoprotein-Enriched Fraction from a Cosmetic Variation of the Longevity Medicine, Gongjin-Dan
by Gwang Jin Lee, Jiwon Park, Hyeon Jun Jeon, Tae Heon Kim, Hyejin Lee, Seongsu Kang, Seung Jin Hwang, Nam Seo Son and Nae-Gyu Kang
Cosmetics 2025, 12(3), 91; https://doi.org/10.3390/cosmetics12030091 - 1 May 2025
Viewed by 963
Abstract
This study deals with the extraction of active compounds for a formula (Angelica gigas, Cornus officinalis, Ganoderma lucidum, Thymus vulgaris, and Asparagus cochinchinensis) and the evaluation of its skin anti-aging properties. This formulation was inspired by the [...] Read more.
This study deals with the extraction of active compounds for a formula (Angelica gigas, Cornus officinalis, Ganoderma lucidum, Thymus vulgaris, and Asparagus cochinchinensis) and the evaluation of its skin anti-aging properties. This formulation was inspired by the oriental medicine Gongjin-dan (Angelica gigas, Cornus officinalis, deer antler, and musk), which has been used as a restorative drug for longevity. Enzyme-based extraction and chemical purification were used to obtain a mixed fraction (GEF) enriched in glycopeptides and glycoproteins from the five herbal materials. The chemical characteristics of GEF, including the carbohydrate groups attached to the peptides and proteins, the total carbohydrate and protein contents, and the composition of monosaccharides and amino acids were determined. The chemical characteristics that were significantly different from those of the extract, generally prepared in the same ratio, were the abundance of glycopeptides and glycoproteins and the high proportions of conditionally essential amino acids (51.0%) and acidic/basic amino acids (67.7%). These are necessary components for strengthening the skin layers against aging. The in vitro skin anti-aging properties of GEF on human fibroblasts (HS68), keratinocytes (HaCaT), and adipose-derived mesenchymal stem cells (ADMSCs) were evaluated. It was found that MMP-1 gene expression was inhibited (18–28%) and fibrillin-1 protein (23–37%) was restored contrary to the effect of UV irradiation. COL1A1 and COL4A1 gene expression (25–35%), HAS2 gene expression (22–213%), and adipogenesis (15%) were facilitated. These results demonstrate the potential of GEF as a raw material for skin anti-aging and reinforce the scientific evidence supporting a traditional medicine with a long history. Full article
(This article belongs to the Section Cosmetic Dermatology)
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24 pages, 4652 KiB  
Article
Anti-Inflammatory Effects of Hyeonggaeyeongyo-tang: Evidence from In Vitro and In Vivo Studies
by Keun Hee Lee, Min Hee Kim and Hae Jeong Nam
Life 2025, 15(4), 587; https://doi.org/10.3390/life15040587 - 2 Apr 2025
Viewed by 544
Abstract
Hyeonggaeyeongyo-tang (HGYGT), a traditional herbal formula, is used to treat inflammatory otorhinolaryngological diseases such as otitis media and sinusitis. In this study, we investigated the anti-inflammatory effects of HGYGT in LPS-stimulated RAW 264.7 cells (in vitro) and a carrageenan (CA)-induced rat paw edema [...] Read more.
Hyeonggaeyeongyo-tang (HGYGT), a traditional herbal formula, is used to treat inflammatory otorhinolaryngological diseases such as otitis media and sinusitis. In this study, we investigated the anti-inflammatory effects of HGYGT in LPS-stimulated RAW 264.7 cells (in vitro) and a carrageenan (CA)-induced rat paw edema model (in vivo). In LPS-stimulated RAW 264.7 cells, treatment with HGYGT (100 and 300 μg/mL) significantly reduced nitric oxide (NO) production by 24.5% and 51.3%, respectively (p < 0.05, p < 0.01). It also significantly suppressed the production of PGE2 (49.8%), IL-1β (42.7%), IL-6 (45.6%), and TNF-α (47.2%) at 300 μg/mL (p < 0.01). A Western blot analysis confirmed that HGYGT (300 μg/mL) significantly downregulated iNOS and COX-2 expression by 58.4% and 53.1%, respectively, while COX-1 remained unaffected. And HGYGT treatment at 300 μg/mL markedly inhibited NF-κB activation by 44.9% (p < 0.01). Furthermore, HGYGT selectively inhibited JNK phosphorylation by 46.7% (p < 0.01), without significantly affecting ERK1/2 or p38 MAPKs. In the CA-induced rat paw edema model, oral administration of HGYGT (1.0 g/kg) reduced paw swelling by 31.5% at 4 h post-injection (p < 0.01) and significantly decreased iNOS expression in inflamed paw tissues by 43.2% (p < 0.01). A histological analysis revealed that HGYGT (1.0 g/kg) reduced inflammatory cell infiltration by 39.6% in the affected tissue (p < 0.05), demonstrating its anti-inflammatory potential. Our findings demonstrate that HGYGT exerts anti-inflammatory effects by suppressing the JNK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 cells, reducing the production of inflammatory mediators. Notably, HGYGT selectively inhibits COX-2 without affecting COX-1 and preferentially suppresses the JNK pathway. Moreover, its in vivo anti-inflammatory effects were confirmed through iNOS inhibition and histopathological analysis. These findings provide robust scientific evidence supporting the traditional use of HGYGT and its anti-inflammatory properties. Full article
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16 pages, 2774 KiB  
Article
Gagam-Palmultang Restores Immune Homeostasis and T Lymphocyte Activation in a Cyclophosphamide-Induced Immunosuppression Mouse Model
by Jin Young Hong, Bo Ram Choi, Doo Ri Park, Jee Eun Yoon, Ji Yun Shin, Yoon Jae Lee and In-Hyuk Ha
Appl. Sci. 2025, 15(6), 3235; https://doi.org/10.3390/app15063235 - 16 Mar 2025
Viewed by 669
Abstract
Gagam-palmultang (PMT), a traditional Korean herbal formula, has been used to treat various conditions; however, its immunomodulatory potential remains unclear. Our objective was to assess the immunomodulatory effects of PMT in an immunosuppression mouse model. In vitro, we assessed interleukin (IL)-10 production in [...] Read more.
Gagam-palmultang (PMT), a traditional Korean herbal formula, has been used to treat various conditions; however, its immunomodulatory potential remains unclear. Our objective was to assess the immunomodulatory effects of PMT in an immunosuppression mouse model. In vitro, we assessed interleukin (IL)-10 production in concanavalin A (Con A)-stimulated mouse splenocytes using real-time polymerase chain reaction and enzyme-linked immunosorbent assays. In vivo, C57BL/6 mice were intraperitoneally administered cyclophosphamide (CPA) to induce immunosuppression, followed by the oral administration of PMT (100 or 200 mg/kg) once daily for 14 days to evaluate its effects on T lymphocyte activation and immune function restoration. Immune function was evaluated via flow cytometric analysis of CD4+ and CD8+ T cells, thymus index measurements, thymic histopathology, and hematological analysis of white blood cell, monocyte, lymphocyte, neutrophil, and eosinophil counts. PMT significantly increased IL-10 production in Con A-stimulated splenocytes. In immunosuppressed mice, PMT restored the thymus index, improved thymic histopathology, and enhanced hematological parameters. Flow cytometry showed a significant increase in CD3e+CD4+ and CD3e+CD8+ T lymphocytes, and histological evaluation revealed increased CD3+ lymphocytes in the thymus. These findings suggest that PMT enhances T lymphocyte activation and restores immune homeostasis under immunosuppressive conditions, demonstrating its potential as a herbal immunomodulatory agent. Full article
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16 pages, 70002 KiB  
Article
Safety Evaluation for Acute and Chronic Oral Toxicity of Maha Pigut Triphala Contains Three Medicinal Fruits in Sprague-Dawley Rats
by Supaporn Intatham, Weerakit Taychaworaditsakul, Parirat Khonsung, Sunee Chansakaow, Kanjana Jaijoy, Nirush Lertprasertsuke, Noppamas Soonthornchareonnon and Seewaboon Sireeratawong
Biology 2024, 13(12), 1005; https://doi.org/10.3390/biology13121005 - 2 Dec 2024
Viewed by 1383
Abstract
Maha Pigut Triphala is the herbal mixture of three fruits consisting of T. bellirica, T. chebula, and E. officinalis also known as P. emblica. Humans regularly eat the fresh fruits of these plants on a daily basis. Maha Pigut Triphala [...] Read more.
Maha Pigut Triphala is the herbal mixture of three fruits consisting of T. bellirica, T. chebula, and E. officinalis also known as P. emblica. Humans regularly eat the fresh fruits of these plants on a daily basis. Maha Pigut Triphala is one of the widely known herbal medicinal formulas used in traditional Thai medicine. Besides studying pharmacological properties, attention should also be paid to the safety and toxicity studies of herbal medicines. The objective of the present study was to evaluate the acute and chronic oral toxicity of Maha Pigut Triphala (2:1:3) in Sprague-Dawley rats. A single dose of Maha Pigut Triphala at a concentration of 5000 mg/kg body weight was administered orally to female rats in the acute oral toxicity study. In the chronic oral toxicity study, male and female rats were treated with various concentrations of Maha Pigut Triphala (600, 1200, and 2400 mg/kg body weight) once daily for 270 consecutive days. The presence of abnormalities in the symptoms and behavior of the rats were observed and recorded throughout the experiment. Additionally, body weight, organ weight, and mortality were recorded. At the end of the study, blood samples were collected for hematological and blood chemistry analysis, while the internal organs were evaluated for gross pathological and histopathological changes. The acute oral toxicity study revealed no mortality and abnormal symptoms or behavior in Maha Pigut Triphala-treated rats. Moreover, gross pathological and histopathological findings did not reveal any abnormalities in the internal organs. In the chronic oral toxicity evaluation, although there were negligible changes in body weight, organ weight, and hematological and blood chemistry parameters in rats treated with Maha Pigut Triphala for 270 days, no behavioral or gross pathological and histopathological abnormalities were observed. Overall, the results of this study demonstrate that Maha Pigut Triphala (2:1:3) neither causes acute nor chronic oral toxicity in rats, proposing the safety of this herbal formula in animals prior to human trials and use. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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30 pages, 19257 KiB  
Article
An Investigation of the Effect of the Traditional Naxi Herbal Formula Against Liver Cancer Through Network Pharmacology, Molecular Docking, and In Vitro Experiments
by Xiuxiang Yan, Angkhana Inta, Xuefei Yang, Hataichanok Pandith, Terd Disayathanoowat and Lixin Yang
Pharmaceuticals 2024, 17(11), 1429; https://doi.org/10.3390/ph17111429 - 25 Oct 2024
Cited by 2 | Viewed by 11656
Abstract
Background/Objectives: The formula Chong-Lou-Yao-Fang (CLYF) is an herbal medicinal formulation developed by the indigenous Naxi people for treating liver cancer. This study was to reveal the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment. Methods: Network pharmacology, [...] Read more.
Background/Objectives: The formula Chong-Lou-Yao-Fang (CLYF) is an herbal medicinal formulation developed by the indigenous Naxi people for treating liver cancer. This study was to reveal the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment. Methods: Network pharmacology, microarray data analysis, survival analysis, and molecular docking were employed to predict potential compounds, targets, and pathways for the treatment of liver cancer. In vitro experiments and Western blot validation were conducted to confirm these predictions. Results: 35 key compounds and 20 core targets were screened from CLYF, involving signaling pathways for PI3K–Akt, MAPK, hepatitis B and C, which were effective for liver cancer treatment. Microarray data analysis and survival analysis indicated that EGFR and TP53 serve as promising biomarkers for diagnosis and prognosis in liver cancer. Molecular docking revealed stable binding between EGFR, TP53, and AKT1 with active ingredients. Cell experiments confirmed that CLYF-A suppressed cell proliferation, induced apoptosis, and caused cell cycle arrest in HepG2 cells, which were associated with a loss of mitochondrial membrane potential. Compared to the control group, the relative protein expression levels of EGFR and AKT1 significantly decreased following treatment with CLYF-A, while TP53 levels increased significantly. Conclusions: Verification of the anticancer activity of CLYF and its potential mechanisms may have important implications for anticancer therapies. Our results may provide a scientific basis for the clinical use of CLYF for cancer treatment and have important implications for developing pharmaceutical preparations, which also need more pharmacological experiments, clinical experiments, and in vivo experiments. Full article
(This article belongs to the Section Pharmacology)
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16 pages, 32828 KiB  
Article
The Cardioprotective Potential of Herbal Formulas in Myocardial Infarction-Induced Heart Failure through Inhibition of JAK/STAT3 Signaling and Improvement of Cardiac Function
by Youn-Jae Jang, Hye-Yoom Kim, Se-Won Na, Mi-Hyeon Hong, Jung-Joo Yoon, Ho-Sub Lee and Dae-Gill Kang
Pharmaceuticals 2024, 17(9), 1132; https://doi.org/10.3390/ph17091132 - 27 Aug 2024
Cited by 1 | Viewed by 1539
Abstract
Myocardial infarction (MI) is a leading cause of heart failure, characterized by adverse cardiac remodeling. This study evaluated the cardioprotective potential of Dohongsamul-tang (DHT), a traditional Korean herbal formula, in a rat model of MI-induced heart failure. Rats underwent left anterior descending (LAD) [...] Read more.
Myocardial infarction (MI) is a leading cause of heart failure, characterized by adverse cardiac remodeling. This study evaluated the cardioprotective potential of Dohongsamul-tang (DHT), a traditional Korean herbal formula, in a rat model of MI-induced heart failure. Rats underwent left anterior descending (LAD) artery ligation and were treated with either 100 mg/kg or 200 mg/kg of DHT daily for 8 weeks. DHT treatment significantly improved cardiac function, as evidenced by increased ejection fraction (EF) from 62.1% to 70.1% (100 mg/kg) and fractional shortening (FS) from 32.3% to 39.4% (200 mg/kg) compared to the MI control group. Additionally, DHT reduced infarct size by approximately 63.3% (from 60.0% to 22.0%) and heart weight by approximately 16.7% (from 3.6 mg/g to 3.0 mg/g), and significantly decreased levels of heart failure biomarkers: LDH was reduced by 37.6% (from 1409.1 U/L to 879.1 U/L) and CK-MB by 47.6% (from 367.3 U/L to 192.5 U/L). Histological analysis revealed a reduction in left ventricle (LV) fibrosis by approximately 50% (from 24.0% to 12.0%). At the molecular level, DHT inhibited the expression of phospho-JAK by 75% (from 2-fold to 0.5-fold), phospho-STAT3 by 30.8% (from 1.3-fold to 0.9-fold), Bax/Bcl-2 by 56.3% (from 3.2-fold to 1.4-fold), and caspase-3 by 46.3% (from 1.23-fold to 0.66-fold). These results suggest that DHT exerts cardioprotective effects by modulating the JAK/STAT3 signaling pathway, highlighting its potential as a therapeutic option for heart failure. Full article
(This article belongs to the Special Issue Plant-Based Therapies for Circulatory Disorders)
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15 pages, 1342 KiB  
Article
Qualitative and Quantitative Analysis of Phytochemicals in Sayeok-Tang via UPLC-Q-Orbitrap-MS and UPLC-TQ-MS/MS
by Yu Jin Kim, Seol Jang and Youn-Hwan Hwang
Pharmaceuticals 2024, 17(9), 1130; https://doi.org/10.3390/ph17091130 - 27 Aug 2024
Cited by 3 | Viewed by 1630
Abstract
Sayeok-tang (SYT) is a traditional herbal formula comprising three medicinal herbs: Glycyrrhiza uralensis, Zingiber officinale, and Aconitum carmichaeli. Several studies have employed liquid chromatography-mass spectrometry (LC-MS) to qualitatively analyze the components and metabolites of SYT in vitro and in vivo; [...] Read more.
Sayeok-tang (SYT) is a traditional herbal formula comprising three medicinal herbs: Glycyrrhiza uralensis, Zingiber officinale, and Aconitum carmichaeli. Several studies have employed liquid chromatography-mass spectrometry (LC-MS) to qualitatively analyze the components and metabolites of SYT in vitro and in vivo; however, studies on quantitative analysis of SYT, which is important for quality control, are absent or limited to only a few components. In this study, ultrahigh-performance liquid chromatography coupled with quadrupole (UPLC-Q)-Orbitrap-MS was used to screen the phytochemicals of SYT, revealing a total of 42 compounds. Among them, 24 compounds were simultaneously quantified within 20 min via UPLC-TQ-MS/MS in the multiple reaction monitoring mode. The developed analytical method was validated for its linearity (r2 ≥ 0.9992), precision (0.36–2.96%), accuracy (−6.52–4.64%), and recovery (94.39–119.07%) for all analytes, exhibiting acceptable results. The validated method was applied in the analysis of SYT extracts, and the 24 compounds were quantified in the range of 0.004–6.882 mg/g (CV ≤ 3.746%). Among them, liquiritin apioside (6.870–6.933 mg/g), glycyrrhizic acid (5.418–5.540 mg/g), and liquiritin (1.303–1.331 mg/g) from G. uralensis were identified as the relatively abundant compounds. The presented validated analytical method is highly promising for the comprehensive quality control of SYT, offering fast, highly sensitive, and reliable analysis. Full article
(This article belongs to the Special Issue Advances in Mass Spectrometry Metrology in Pharmaceutical Sciences)
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23 pages, 10953 KiB  
Article
Integrating 16S rRNA Sequencing, Microflora Metabolism, and Network Pharmacology to Investigate the Mechanism of SBL in Alleviating HDM-Induced Allergic Rhinitis
by Peiting Li, Sharon Sze-Man Hon, Miranda Sin-Man Tsang, Lea Ling-Yu Kan, Andrea Yin-Tung Lai, Ben Chung-Lap Chan, Ping-Chung Leung and Chun-Kwok Wong
Int. J. Mol. Sci. 2024, 25(16), 8655; https://doi.org/10.3390/ijms25168655 - 8 Aug 2024
Cited by 1 | Viewed by 4323
Abstract
Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a [...] Read more.
Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis. Full article
(This article belongs to the Special Issue Progression of Allergy and Immune Response)
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