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Pueraria lobata (Willd.) Ohwi is a traditional medicinal herb that has been extensively used in Chinese medicine for various therapeutic purposes. In this study, twelve chemical constituents were isolated from the roots of P. lobata, comprising three puerosides (compounds 1–3), six alkaloids (compounds 4–9), and three additional compounds (compounds 10–12). Notably, compound 1 (4R-pueroside B) was identified as a novel compound. The structures of all compounds were elucidated using a range of spectroscopic techniques, including CD spectroscopy for the first-time determination of the absolute configurations of pueroside B isomers (compounds 1 and 2). Enzyme inhibition assays revealed that, with the exception of compound 2, all isolated compounds exhibited varying degrees of α-glucosidase and α-amylase inhibitory activity. Remarkably, compound 12 demonstrated IC50 values of 23.25 μM for α-glucosidase inhibition and 27.05 μM for α-amylase inhibition, which are superior to those of the positive control, acarbose (27.05 μM and 36.68 μM, respectively). Additionally, compound 11 exhibited inhibitory activity against α-glucosidase and α-amylase comparable to the positive control, acarbose. Molecular docking studies indicated that compound 12 interacts with the active sites of the enzymes via hydrogen bonds, van der Waals forces, and hydrophobic interactions, which likely contribute to their inhibitory effects. These findings suggest that the chemical constituents of P. lobata could be potential natural sources of α-amylase and α-glucosidase inhibitors, with compound 12 being particularly promising for further investigation. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP's efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1β, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies. [ABSTRACT FROM AUTHOR]

The interaction between environmental stressors, such as cold exposure, and immune function significantly impacts human health. Research on effective therapeutic strategies to combat cold-induced immunosuppression is limited, despite its importance. In this study, we aim to investigate whether traditional herbal medicine can counteract cold-induced immunosuppression. We previously demonstrated that cold exposure elevated immunoglobulin G (IgG) levels in mice, similar to the effects of intravenous immunoglobulin (IVIg) treatments. This cold-induced rise in circulating IgG was mediated by the renin–angiotensin–aldosterone system and linked to vascular constriction. In our mouse model, the cold-exposed groups (4 °C) showed significantly elevated plasma IgG levels and reduced bacterial clearance compared with the control groups maintained at room temperature (25 °C), both indicative of immunosuppression. Using this model, with 234 mice divided into groups of 6, we investigated the potential of tanshinone IIA, an active compound in Salvia miltiorrhiza ethanolic root extract (SMERE), in alleviating cold-induced immunosuppression. Tanshinone IIA and SMERE treatments effectively normalized elevated plasma IgG levels and significantly improved bacterial clearance impaired by cold exposure compared with control groups injected with a vehicle control, dimethyl sulfoxide. Notably, bacterial clearance, which was impaired by cold exposure, showed an approximately 50% improvement following treatment, restoring immune function to levels comparable to those observed under normal temperature conditions (25 °C, p < 0.05). These findings highlight the therapeutic potential of traditional herbal medicine in counteracting cold-induced immune dysregulation, offering valuable insights for future strategies aimed at modulating immune function in cold environments. Further research could focus on isolating tanshinone IIA and compounds present in SMERE to evaluate their specific roles in mitigating cold-induced immunosuppression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve. [ABSTRACT FROM AUTHOR]

An approach based on the heat stress and microbial stress model of the medicinal plant Sparganium stoloniferum was proposed to elucidate the regulation and mechanism of bioactive phenol accumulation. This method integrates LC–MS/MS analysis, 16S rRNA sequencing, RT–qPCR, and molecular assays to investigate the regulation of phenolic metabolite biosynthesis in S. stoloniferum rhizome (SL) under stress. Previous research has shown that the metabolites and genes involved in phenol biosynthesis correlate to the upregulation of genes involved in plant–pathogen interactions. High-temperature and the presence of Pseudomonas bacteria were observed alongside SL growth. Under conditions of heat stress or Pseudomonas bacteria stress, both the metabolites and genes involved in phenol biosynthesis were upregulated. The regulation of phenol content and phenol biosynthesis gene expression suggests that phenol-based chemical defense of SL is stimulated under stress. Furthermore, the rapid accumulation of phenolic substances relied on the consumption of amino acids. Three defensive proteins, namely Ss4CL, SsC4H, and SsF3′5′H, were identified and verified to elucidate phenol biosynthesis in SL. Overall, this study enhances our understanding of the phenol-based chemical defense of SL, indicating that bioactive phenol substances result from SL's responses to the environment and providing new insights for growing the high-phenol-content medicinal herb SL. [ABSTRACT FROM AUTHOR]

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN-γ and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer. [ABSTRACT FROM AUTHOR]

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes. [ABSTRACT FROM AUTHOR]

Oxytocin, a significant pleiotropic neuropeptide, regulates psychological stress adaptation and social communication, as well as peripheral actions, such as uterine contraction and milk ejection. Recently, a Japanese Kampo medicine called Kamikihito (KKT) has been reported to stimulate oxytocin neurons to induce oxytocin secretion. Two-pore-domain potassium channels (K2P) regulate the resting potential of excitable cells, and their inhibition results in accelerated depolarization that elicits neuronal and endocrine cell activation. We assessed the effects of KKT and 14 of its components on a specific K2P, the potassium channel subfamily K member 2 (TREK-1), which is predominantly expressed in oxytocin neurons in the central nervous system (CNS). KKT inhibited the activity of TREK-1 induced via the channel activator ML335. Six of the 14 components of KKT inhibited TREK-1 activity. Additionally, we identified that 22 of the 41 compounds in the six components exhibited TREK-1 inhibitory effects. In summary, several compounds included in KKT partially activated oxytocin neurons by inhibiting TREK-1. The pharmacological effects of KKT, including antistress effects, may be partially mediated through the oxytocin pathway. [ABSTRACT FROM AUTHOR]

As the global population ages, the prevalence of Parkinson's disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer's disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment. [ABSTRACT FROM AUTHOR]

Sauropus androgynus (S. androgynus) (2n = 4x = 52) is one of the most popular functional leafy vegetables in South and Southeast Asia. With its rich nutritional and pharmaceutical values, it has traditionally had widespread use for dietary and herbal purposes. Here, the genome of S. androgynus was sequenced and assembled, revealing a genome size of 1.55 Gb with 26 pseudo-chromosomes. Phylogenetic analysis traced back the divergence of Sauropus from Phyllanthus to approximately 29.67 million years ago (Mya). Genome analysis revealed that S. androgynus polyploidized around 20.51 Mya and shared a γ event about 132.95 Mya. Gene function analysis suggested that the expansion of pathways related to phloem development, lignin biosynthesis, and photosynthesis tended to result in the morphological differences among species within the Phyllanthaceae family, characterized by varying ploidy levels. The high accumulation of ascorbic acid in S. androgynus was attributed to the high expression of genes associated with the L-galactose pathway and recycling pathway. Moreover, the expanded gene families of S. androgynus exhibited multiple biochemical pathways associated with its comprehensive pharmacological activity, geographic adaptation and distinctive pleasurable flavor. Altogether, our findings represent a crucial genomic asset for S. androgynus, casting light on the intricate ploidy within the Phyllanthaceae family. [ABSTRACT FROM AUTHOR]

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP’s efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1β, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies.

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after incubation with both DOX and BC was significantly increased (~100%) compared to the control. Treatment with DOX altered the potential of MCF-7 cells to form colonies; however, coincubation with BC did not affect this process. In vivo, PET-CT imaging showed that combined treatment of DOX and BC induced a significant reduction in both metabolic activity (29%) and angiogenesis (32%). Both DOX and BC treatments inhibited tumor growth by 20% and 12%, respectively, and combined by 57%, vs. control. We successfully demonstrated that BC increases cytotoxic effects of DOX, resulting in a significant reduction in tumor size. Further studies regarding drug transport and tumor growth biomarkers are necessary to establish the underlying mechanism and potential clinical use of BC in breast cancer patients. [ABSTRACT FROM AUTHOR]

Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai—a naturally growing species in South Korea—and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Ardisiae Crenatae Radix is an ethnic medicinal herb with good anti-inflammatory activity. Ardisiacrispin B is one of the main components in Ardisiae Crenatae Radix extract, with a content of up to 16.27%, and it may be one of the pharmacological components through which Ardisiae Crenatae Radix exerts anti-inflammatory activity. At present, reports on ardisiacrispin B mainly focus on anti-tumor effects, and there have been no reports on anti-inflammatory activities. As a triterpenoid saponin, due to its large molecular weight and complex structure, the composition of substances that function in the body may include other forms after metabolism, in addition to compounds with original structures. Exploring the anti-inflammatory effects on the prototypes and metabolites of the compound may provide a more comprehensive response to the characteristics of ardisiacrispin B's anti-inflammatory action. In this study, ardisiacrispin B was analyzed for metabolites to explore its metabolic processes in vivo. Subsequently, the anti-inflammatory effects of the prototypes and metabolites were further analyzed through network pharmacology, with the expectation of discovering the signaling metabolic pathways through which they may act. Finally, the anti-inflammatory effects of ardisiacrispin B in vitro and the effects on key signaling pathways at the protein level were explored. The results of this study showed that the isolated compounds were confirmed to be ardisiacrispin B. After the metabolite analysis, a total of 26 metabolites were analyzed, and the metabolism process in rats mainly involves oxidation, dehydration, glucuronide conjugation, and others. Speculation as to the anti-inflammatory molecular mechanisms of the prototypes and metabolites of ardisiacrispin B revealed that it may exert its anti-inflammatory effects mainly by affecting the PI3K-AKT pathway. Further anti-inflammatory mechanisms demonstrated that ardisiacrispin B had a good anti-inflammatory effect on LPS-induced RAW264.7 cells and a strong inhibitory effect on NO, TNF-α, and IL-1β release in cells. Furthermore, it had significant inhibitory effects on the expression of PI3K, P-PI3K, AKT, and P-AKT. This study supplements the gaps in the knowledge on the in vivo metabolic process of ardisiacrispin B and explores its anti-inflammatory mechanism, providing an experimental basis for the development and utilization of pentacyclic triterpenoids. [ABSTRACT FROM AUTHOR]

Members of the family Coronaviridae cause diseases in mammals, birds, and wildlife (bats), some of which may be transmissible to humans or specific to humans. In the human population, they can cause a wide range of diseases, mainly affecting the respiratory and digestive systems. In the scientific databases, there are huge numbers of research articles about the antiviral, antifungal, antibacterial, antiviral, and anthelmintic activities of medicinal herbs and crops with different ethnobotanical backgrounds. The subject of our research is the antiviral effect of isolated saponins, a purified saponin mixture, and a methanol extract of Astragalus glycyphyllos L. In the studies conducted for the cytotoxic effect of the substances, CC50 (cytotoxic concentration 50) and MTC (maximum tolerable concentration) were determined by the colorimetric method (MTT assay). The virus was cultured in the MDBK cell line. As a result of the experiments carried out on the influence of substances on viral replication (using MTT-based colorimetric assay for detection of human Coronavirus replication inhibition), it was found that the extract and the purified saponin mixture inhibited 100% viral replication. The calculated selective indices are about 13 and 18, respectively. The obtained results make them promising for a preparation with anti-Coronavirus action. [ABSTRACT FROM AUTHOR]

Lonicerae Japonicae Flos (LJF) has been globally applied as an herbal medicine and tea. A number of reports recently revealed fungal and mycotoxin contamination in medicinal herbs. It is essential to analyze the fungal community in LJF to provide an early warning for supervision. In this study, the fungal community in LJF samples was identified through DNA metabarcoding. A total of 18 LJF samples were collected and divided based on the collection areas and processing methods. The results indicated that Ascomycota was the dominant phylum. At the genus level, Rhizopus was the most abundant, followed by Erysiphe and Fusarium. Ten pathogenic fungi were detected among the 41 identified species. Moreover, Rhizopus, Fusarium, and Aspergillus had lower relative abundances in LJF samples under oven drying than under other processing methods. This work is expected to provide comprehensive knowledge of the fungal community in LJF and a theoretical reference for enhanced processing methods in practical manufacturing. [ABSTRACT FROM AUTHOR]

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN-γ and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer.

Oxytocin, a significant pleiotropic neuropeptide, regulates psychological stress adaptation and social communication, as well as peripheral actions, such as uterine contraction and milk ejection. Recently, a Japanese Kampo medicine called Kamikihito (KKT) has been reported to stimulate oxytocin neurons to induce oxytocin secretion. Two-pore-domain potassium channels (K2P) regulate the resting potential of excitable cells, and their inhibition results in accelerated depolarization that elicits neuronal and endocrine cell activation. We assessed the effects of KKT and 14 of its components on a specific K2P, the potassium channel subfamily K member 2 (TREK-1), which is predominantly expressed in oxytocin neurons in the central nervous system (CNS). KKT inhibited the activity of TREK-1 induced via the channel activator ML335. Six of the 14 components of KKT inhibited TREK-1 activity. Additionally, we identified that 22 of the 41 compounds in the six components exhibited TREK-1 inhibitory effects. In summary, several compounds included in KKT partially activated oxytocin neurons by inhibiting TREK-1. The pharmacological effects of KKT, including antistress effects, may be partially mediated through the oxytocin pathway.

Spirodela polyrhiza (L.) SCHLEID. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in S. polyrhiza and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of S. polyrhiza (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (<−8 kcal/mol) and IL-6 (<−6 kcal/mol). Our in vivo studies showed that topical EESP ameliorated DNFB-induced skin lesions and histopathological abnormalities, and reduced the levels of TNF-α, interferon (IFN)-ɣ, IL-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues. In conclusion, our findings suggest the potential for dermatological applications of S. polyrhiza and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides. [ABSTRACT FROM AUTHOR]

R2R3-MYB transcription factors (TFs) form one of the most important TF families involved in regulating various physiological functions in plants. The heartwood of Dalbergia odorifera is a kind of high-grade mahogany and valuable herbal medicine with wide application. However, the role of R2R3-MYB genes in the growth and development of D. odorifera, especially their relevance to heartwood formation, has not been revealed. A total of 126 R2R3-MYBs were screened from the D. odorifera genome and named DodMYB1-126 based on their location on 10 chromosomes. The collinearity results showed that purification selection was the main driving force for the evolution of the R2R3-MYB TFs family, and whole genome/fragment replication event was the main form for expanding the R2R3-MYB family, generating a divergence of gene structure and function. Comparative phylogenetic analysis classified the R2R3-MYB TFs into 33 subfamilies. S3-7,10,12-13,21 and N4-7 were extensively involved in the metabolic process; S9,13,16-19,24-25 and N1-3,8 were associated with the growth and development of D. odorifera. Based on the differential transcriptional expression levels of R2R3-MYBs in different tissues, DodMYB32, DodMYB55, and DodMYB89 were tentatively screened for involvement in the regulatory process of heartwood. Further studies have shown that the DodMYB89, localized in the nucleus, has transcriptional activation activity and is involved in regulating the biosynthesis of the secondary metabolites of heartwood by activating the promoters of the structural genes DodI2'H and DodCOMT. This study aimed to comprehensively analyze the functions of the R2R3-MYB TFs and screen for candidate genes that might be involved in heartwood formation of D. odorifera. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, effective treatments or expanded diagnostic or prognostic markers for AML have not yet been identified. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSCs) consist of hematopoietic stem cells (HSCs) and cancer cells transformed by a complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSCs dormancy and the diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML are discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSCs, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveal that microRNAs are a unique factor for LSCs. Multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSCs, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predict that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and could prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes achievable with Network Pharmacology research. [ABSTRACT FROM AUTHOR]

Tubeimoside-1 (TBMS-1), a traditional Chinese medicinal herb, is commonly used as an anti-cancer agent. In this study, we aimed to investigate its effect on the sensitization of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Our results revealed that even though monotherapy using TBMS-1 or TRAIL at sublethal concentrations did not affect cancer cell death, combination therapy using TBMS-1 and TRAIL increased apoptotic cell death. Mechanistically, TBMS-1 destabilized c-FLIP expression by downregulating STAMBPL1, a deubiquitinase (DUB). Specifically, when STAMBPL1 and c-FLIP bound together, STAMBPL1 deubiquitylated c-FLIP. Moreover, STAMBPL1 knockdown markedly increased sensitivity to TRAIL by destabilizing c-FLIP. These findings were further confirmed in vivo using a xenograft model based on the observation that combined treatment with TBMS-1 and TRAIL decreased tumor volume and downregulated STAMBPL1 and c-FLIP expression levels. Overall, our study revealed that STAMBPL1 is essential for c-FLIP stabilization, and that STAMBPL1 depletion enhances TRAIL-mediated apoptosis via c-FLIP downregulation. [ABSTRACT FROM AUTHOR]

Scrophularia ningpoensis, a perennial medicinal plant from the Scrophulariaceae family, is the original species of Scrophulariae Radix (SR) in the Chinese Pharmacopoeia. This medicine is usually deliberately substituted or accidentally contaminated with other closely related species including S. kakudensis, S. buergeriana, and S. yoshimurae. Given the ambiguous identification of germplasm and complex evolutionary relationships within the genus, the complete chloroplast genomes of the four mentioned Scrophularia species were sequenced and characterized. Comparative genomic studies revealed a high degree of conservation in genomic structure, gene arrangement, and content within the species, with the entire chloroplast genome spanning 153,016–153,631 bp in full length, encoding 132 genes, including 80 protein-coding genes, 4 rRNA genes, 30 tRNA genes, and 18 duplicated genes. We identified 8 highly variable plastid regions and 39–44 SSRs as potential molecular markers for further species identification in the genus. The consistent and robust phylogenetic relationships of S. ningpoensis and its common adulterants were firstly established using a total of 28 plastid genomes from the Scrophulariaceae family. In the monophyletic group, S. kakudensis was determined to be the earliest diverging species, succeeded by S. ningpoensis. Meanwhile, S. yoshimurae and S. buergeriana were clustered together as sister clades. Our research manifestly illustrates the efficacy of plastid genomes in identifying S. ningpoensis and its counterfeits and will also contribute to a deeper understanding of the evolutionary processes within Scrophularia. [ABSTRACT FROM AUTHOR]

Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was used as early as about A.D. 25-220 as a remedy. Traditionally, AN was applied for several medicinal functions. However, it was also reported to have toxicological effects. In this review article, we updated recent trends of research in addition to acquire new knowledge about AN. First, the history of AN usage from ancient years was described. Then, the chemical components of AN and their biological functions was compared; arecoline is an especially important compound in AN. AN extract has different effects caused by different components. Thus, the dual effects of AN with pharmacological and toxicological effects were summarized. Finally, we described perspectives, trends and challenges of AN. It will provide the insight of removing or modifying the toxic compounds of AN extractions for enhancing their pharmacological activity to treat several diseases in future applications. [ABSTRACT FROM AUTHOR]

Rhus coriaria Linn is a little plant growing in the Mediterranean basin, including Sicily, where it is known as Sicilian Sumac. Since antiquity, it has been used as a medicinal herb, considering its pharmacological properties and its recognized anti-inflammatory, antioxidant, and antimicrobial effects. Multiple studies have highlighted that the beneficial properties of Sumac extracts depend on the abundance of phytochemicals such as polyphenols, fatty acids, minerals, and fibers. Despite its wide use as a spice, the literature on Sumac effects on humans' health and aging is still scarce. Considering its great nutraceutical potential, Sumac could be used to treat age-related diseases such as those in which the inflammatory process plays a crucial role in manifestation and progression. Thus, Sumac could be an interesting new insight in the biomedical field, especially in aging biomedicine. [ABSTRACT FROM AUTHOR]

Osteoporosis is a metabolic skeletal disease characterized by lowered bone mineral density and quality, which lead to an increased risk of fracture. The aim of this study was to evaluate the anti-osteoporosis effects of a mixture (called BPX) of Cervus elaphus sibiricus and Glycine max (L.) Merrill and its underlying mechanisms using an ovariectomized (OVX) mouse model. BALB/c female mice (7 weeks old) were ovariectomized. From 12 weeks of ovariectomy, mice were administered BPX (600 mg/kg) mixed in a chow diet for 20 weeks. Changes in bone mineral density (BMD) and bone volume (BV), histological findings, osteogenic markers in serum, and bone formation-related molecules were analyzed. Ovariectomy notably decreased the BMD and BV scores, while these were significantly attenuated by BPX treatment in the whole body, femur, and tibia. These anti-osteoporosis effects of BPX were supported by the histological findings for bone microstructure from H&E staining, increased activity of alkaline phosphatase (ALP), but a lowered activity of tartrate-resistant acid phosphatase (TRAP) in the femur, along with other parameters in the serum, including TRAP, calcium (Ca), osteocalcin (OC), and ALP. These pharmacological actions of BPX were explained by the regulation of key molecules in the bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) pathways. The present results provide experimental evidence for the clinical relevance and pharmaceutical potential of BPX as a candidate for anti-osteoporosis treatment, especially under postmenopausal conditions. [ABSTRACT FROM AUTHOR]

Plant roots, due to a high content of natural antioxidants for many years, have been used in herbal medicine. It has been documented that the extract of Baikal skullcap (Scutellaria baicalensis) has hepatoprotective, calming, antiallergic, and anti-inflammatory properties. Flavonoid compounds found in the extract, including baicalein, have strong antiradical activity, which improves overall health and increases feelings of well-being. Plant-derived bioactive compounds with antioxidant activity have for a long time been used as an alternative source of medicines to treat oxidative stress-related diseases. In this review, we summarized the latest reports on one of the most important aglycones with respect to the pharmacological activity and high content in Baikal skullcap, which is 5,6,7-trihydroxyflavone (baicalein). [ABSTRACT FROM AUTHOR]

Hydrogel is a biomaterial widely used in several areas of industry due to its great biocompatibility and adaptability to biological tissues. In Brazil, the Calendula plant is approved by the Ministry of Health as a medicinal herb. It was chosen to be incorporated in the hydrogel formulation because of its anti-inflammatory, antiseptic and healing effects. This study synthesized polyacrylamide hydrogel containing calendula extract and evaluated its efficiency as a bandage for wound healing. The hydrogels were prepared using free radical polymerization and characterized by Scanning Electron Microscopy, swelling analysis and mechanical properties by texturometer. The morphology of the matrices showed large pores and foliaceous structure. In vivo testing, as well as the evaluation of acute dermal toxicity, was conducted using male Wistar rats. The tests indicated efficient collagen fiber production, improved skin repair and no signs of dermal toxicity. Thus, the hydrogel presents compatible properties for the controlled release of calendula extract used as a bandage to promote cicatrization. [ABSTRACT FROM AUTHOR]

The pathophysiology of nonalcoholic steatohepatitis (NASH) is complex, owing to its diverse pathological drivers and, until recently, there were no approved drugs for this disease. Tecomella is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. The administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in western diet sugar water (WDSW) fed mice but had no effect on chow diet normal water (CDNW) fed mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced Endoplasmic Reticulum stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were comparable to saroglitazar, the approved drug used to treat human NASH and the positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH. [ABSTRACT FROM AUTHOR]

Traditional herbal medicines based on natural products play a pivotal role in preventing and managing atherosclerotic diseases, which are among the leading causes of death globally. Monoterpenes are a large class of naturally occurring compounds commonly found in many aromatic and medicinal plants. Emerging evidence has shown that monoterpenes have many biological properties, including cardioprotective effects. Remarkably, an increasing number of studies have demonstrated the therapeutic potential of natural monoterpenes to protect against the pathogenesis of atherosclerosis. These findings shed light on developing novel effective antiatherogenic drugs from these compounds. Herein, we provide an overview of natural monoterpenes' effects on atherogenesis and the underlying mechanisms. Monoterpenes have pleiotropic and multitargeted pharmacological properties by interacting with various cell types and intracellular molecular pathways involved in atherogenesis. These properties confer remarkable advantages in managing atherosclerosis, which has been recognized as a multifaceted vascular disease. We also discuss limitations in the potential clinical application of monoterpenes as therapeutic agents against atherosclerosis. We propose perspectives to give new insights into future preclinical research and clinical practice regarding natural monoterpenes. [ABSTRACT FROM AUTHOR]

Sauropus androgynus (S. androgynus) (2n = 4x = 52) is one of the most popular functional leafy vegetables in South and Southeast Asia. With its rich nutritional and pharmaceutical values, it has traditionally had widespread use for dietary and herbal purposes. Here, the genome of S. androgynus was sequenced and assembled, revealing a genome size of 1.55 Gb with 26 pseudo-chromosomes. Phylogenetic analysis traced back the divergence of Sauropus from Phyllanthus to approximately 29.67 million years ago (Mya). Genome analysis revealed that S. androgynus polyploidized around 20.51 Mya and shared a γ event about 132.95 Mya. Gene function analysis suggested that the expansion of pathways related to phloem development, lignin biosynthesis, and photosynthesis tended to result in the morphological differences among species within the Phyllanthaceae family, characterized by varying ploidy levels. The high accumulation of ascorbic acid in S. androgynus was attributed to the high expression of genes associated with the L-galactose pathway and recycling pathway. Moreover, the expanded gene families of S. androgynus exhibited multiple biochemical pathways associated with its comprehensive pharmacological activity, geographic adaptation and distinctive pleasurable flavor. Altogether, our findings represent a crucial genomic asset for S. androgynus, casting light on the intricate ploidy within the Phyllanthaceae family.

Pyroptosis is an active and ordered form of programmed cell death. The signaling pathways of pyroptosis are mainly divided into canonical pathways mediated by caspase-1 and noncanonical pathways mediated by caspase-11. Cell pyroptosis is characterized by the activation of inflammatory caspases (mainly caspase-1, 4, 5, 11) and cleavage of various members of the Gasdermin family to form membrane perforation components, leading to cell membrane rupture, inflammatory mediators release, and cell death. Moderate pyroptosis is an innate immune response that fights against infection and plays an important role in the occurrence and development of the normal function of the immune system. However, excessive pyroptosis occurs and leads to immune disorders in many pathological conditions. Based on canonical pathways, research on pyroptosis regulation has demonstrated several pyroptotic inhibitors, including small-molecule drugs, natural products, and formulations of traditional Chinese medicines. In this paper, we review the characteristics and molecular mechanisms of pyroptosis, summarize inhibitors of pyroptosis, and propound that herbal medicines should be a focus on the research and development for pyroptosis blockers. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, immune-mediated inflammatory skin disorder. Rheum palmatum L. is a common traditional medicinal herb with anti-inflammatory and immunomodulatory activities. This study aimed to investigate the anti-psoriatic effects of the ethanolic extract from R. palmatum L. (RPE) and its chemical constituents, as well as the mechanisms underlying their therapeutic significance. An imiquimod (IMQ)-induced psoriasis-like mouse model was used to examine the anti-psoriatic effect of RPE in vivo. Network pharmacological analysis was performed to investigate the potential targets and related pathways of the RPE components, including rhein, emodin, chrysophanol, aloe-emodin, and physcion. The anti-inflammatory effects and underlying mechanisms of these components were examined using in vitro models. Topical application of RPE alleviated psoriasis-like symptoms and reduced levels of inflammatory cytokines and proliferation markers in the skin. Network pharmacological analysis revealed that RPE components target 20 genes that are linked to psoriasis-related pathways, such as IL-17, MAPK, and TNF signaling pathways. Among the five components of RPE, rhein and emodin showed inhibitory effects on TNF-α and IL-17 production in EL-4 cells, attenuated the production of CXCL8, CXCL10, CCL20, and MMP9, and reduced proliferation in HaCaT cells. Chrysophanol, aloe-emodin, and physcion were less effective than rhein and emodin in suppressing inflammatory responses and keratinocyte proliferation. The effects of these compounds might occur through the inhibition of the ERK, STAT3, and NF-κB signaling pathways. This study suggested the anti-psoriatic effect of RPE, with rhein and emodin as the main contributors that regulate multiple signaling pathways. [ABSTRACT FROM AUTHOR]

Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is an inflammation-associated common cancer worldwide. Paejang-san and Mori Cortex Radicis have been traditionally used for treating intestinal inflammatory diseases in Korea and China. In the present study, we developed a new herbal formula as an alternative to CRC treatments, which is composed of two main components of Paejangsan (Patriniae Radix (Paejang in Korean) and Coix Seed (Yiyiin in Korean)), and Mori Cortex Radicis (Sangbekpi in Korean) based on the addition and subtraction theory in traditional medicine, hence the name PSY, and explored the potential therapeutic effects of the new formula PSY in human CRC cells by analyzing viability, cell cycle and apoptosis. We found that PSY ethanol extract (EtOH-Ex), but not water extract, significantly suppressed the viability of human CRC cells, and synergistically decreased the cell proliferation compared to each treatment of Patriniae Radix and Coix Seed extract (PY) or Mori Cortex Radicis extract (S), suggesting the combination of PY and S in a 10-to-3 ratio for the formula PSY. PSY EtOH-Ex in the combination ratio reduced cell viability but induced cell cycle arrest at the G2/M and sub-G1 phases as well as apoptosis in CRC cells. In addition, the experimental results of Western blotting, immunofluorescence staining and reporter assays showed that PSY also inhibited STAT3 by reducing its phosphorylation and nuclear localization, which resulted in lowering STAT3-mediated transcriptional activation. In addition, PSY regulated upstream signaling molecules of STAT3 by inactivating JAK2 and Src and increasing SHP1. Moreover, the chemical profiles of PSY from UPLC-ESI-QTOF MS/MS analysis revealed 38 phytochemicals, including seven organic acids, eight iridoids, two lignans, twelve prenylflavonoids, eight fatty acids, and one carbohydrate. Furthermore, 21 potentially bioactive compounds were highly enriched in the PSY EtOH-Ex compared to the water extract. Together, these results indicate that PSY suppresses the proliferation of CRC cells by inhibiting the STAT3 signaling pathway, suggesting PSY as a potential therapeutic agent for treating CRC and 21 EtOH-Ex-enriched phytochemicals as anti-cancer drug candidates which may act by inhibiting STAT3. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is one of the most malignant types of cancer worldwide and has a high incidence and mortality rate in Asian countries. When it comes to treating EC, although primary methods such as chemotherapy and surgery exist, the prognosis remains poor. The purpose of this current research is to review the range of effects that natural products have on cancer by analyzing studies conducted on EC. Fifty-seven studies were categorized into four anti-cancer mechanisms, as well as clinical trials. The studies that were scrutinized in this research were all reported within five years. The majority of the substances reviewed induced apoptosis in EC, acting on a variety of mechanisms. Taken together, this study supports the fact that natural products have the potential to act as a candidate for treating EC. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and studies have revealed its biological behavior in tumor cell proliferation, migration, and adhesion. Herein we provide an overview of the complex biology of the FAK family members and their context-dependent nature. Next, with a focus on cancer, we highlight the activities of FAK signaling in different types of cancer and how knowledge of them is being used for screening natural compounds used in herbal medicine to fight tumor development. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) has pathological hallmarks including amyloid beta (Aβ) plaque formation. Currently approved single-target drugs cannot effectively ameliorate AD. Medicinal herbs and their derived ingredients (MHDIs) have multitarget and multichannel properties, engendering exceptional AD treatment outcomes. This review delineates how in in vivo models MHDIs suppress Aβ deposition by downregulating β- and γ-secretase activities; inhibit oxidative stress by enhancing the antioxidant activities and reducing lipid peroxidation; prevent tau hyperphosphorylation by upregulating protein phosphatase 2A expression and downregulating glycogen synthase kinase-3β expression; reduce inflammatory mediators partly by upregulating brain-derived neurotrophic factor/extracellular signal-regulated protein kinase 1/2-mediated signaling and downregulating p38 mitogen-activated protein kinase (p38 MAPK)/c-Jun N-terminal kinase (JNK)-mediated signaling; attenuate synaptic dysfunction by increasing presynaptic protein, postsynaptic protein, and acetylcholine levels and preventing acetylcholinesterase activity; and protect against neuronal apoptosis mainly by upregulating Akt/cyclic AMP response element-binding protein/B-cell lymphoma 2 (Bcl-2)-mediated anti-apoptotic signaling and downregulating p38 MAPK/JNK/Bcl-2-associated x protein (Bax)/caspase-3-, Bax/apoptosis-inducing factor-, C/EBP homologous protein/glucose-regulated protein 78-, and autophagy-mediated apoptotic signaling. Therefore, MHDIs listed in this review protect against Aβ-induced cognitive decline by inhibiting Aβ accumulation, oxidative stress, tau hyperphosphorylation, inflammation, synaptic damage, and neuronal apoptosis in the cortex and hippocampus during the early and late AD phases. [ABSTRACT FROM AUTHOR]

Spirodela polyrhiza (L.) SCHLEID. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in S. polyrhiza and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of S. polyrhiza (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (S. polyrhiza and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides.

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease’s intricate molecular mechanisms, effective treatments or expanded diagnostic or prognostic markers for AML have not yet been identified. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSCs) consist of hematopoietic stem cells (HSCs) and cancer cells transformed by a complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSCs dormancy and the diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML are discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSCs, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveal that microRNAs are a unique factor for LSCs. Multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSCs, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predict that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and could prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes achievable with Network Pharmacology research.

Jasmonic acid (JA) is a vital plant hormone that performs a variety of critical functions for plants. Salvia miltiorrhiza Bunge (S. miltiorrhiza), also known as Danshen, is a renowned traditional Chinese medicinal herb. However, no thorough and systematic analysis of JA biosynthesis genes in S. miltiorrhiza exists. Through genome-wide prediction and molecular cloning, 23 candidate genes related to JA biosynthesis were identified in S. miltiorrhiza. These genes belong to four families that encode lipoxygenase (LOX), allene oxide synthase (AOS), allene oxide cyclase (AOC), and 12-OPDA reductase3 (OPR3). It was discovered that the candidate genes for JA synthesis of S. miltiorrhiza were distinct and conserved, in contrast to related genes in other plants, by evaluating their genetic structures, protein characteristics, and phylogenetic trees. These genes displayed tissue-specific expression patterns concerning to methyl jasmonate (MeJA) and wound tests. Overall, the results of this study provide valuable information for elucidating the JA biosynthesis pathway in S. miltiorrhiza by comprehensive and methodical examination. [ABSTRACT FROM AUTHOR]

Dendrobium sinense, an endemic medicinal herb in Hainan Island, is rich in bibenzyls. However, the key rate-limited enzyme involved in bibenzyl biosynthesis has yet to be identified in D. sinense. In this study, to explore whether there is a significant difference between the D. sinense tissues, the total contents of bibenzyls were determined in roots, pseudobulbs, and leaves. The results indicated that roots had higher bibenzyl content than pseudobulbs and leaves. Subsequently, transcriptomic sequencings were conducted to excavate the genes encoding type III polyketide synthase (PKS). A total of six D. sinense PKS (DsPKS) genes were identified according to gene function annotation. Phylogenetic analysis classified the type III DsPKS genes into three groups. Importantly, the c93636.graph_c0 was clustered into bibenzyl synthase (BBS) group, named as D. sinense BBS (DsBBS). The expression analysis by FPKM and RT-qPCR indicated that DsBBS showed the highest expression levels in roots, displaying a positive correlation with bibenzyl contents in different tissues. Thus, the recombinant DsBBS-HisTag protein was constructed and expressed to study its catalytic activity. The molecular weight of the recombinant protein was verified to be approximately 45 kDa. Enzyme activity analysis indicated that the recombinant DsBBS-HisTag protein could use 4-coumaryol-CoA and malonyl-CoA as substrates for resveratrol production in vitro. The Vmax of the recombinant protein for the resveratrol production was 0.88 ± 0.07 pmol s−1 mg−1. These results improve our understanding with respect to the process of bibenzyl biosynthesis in D. sinense. [ABSTRACT FROM AUTHOR]

Osteoporosis is a metabolic skeletal disease characterized by lowered bone mineral density and quality, which lead to an increased risk of fracture. The aim of this study was to evaluate the anti-osteoporosis effects of a mixture (called BPX) of Cervus elaphus sibiricus and Glycine max (L.) Merrill and its underlying mechanisms using an ovariectomized (OVX) mouse model. BALB/c female mice (7 weeks old) were ovariectomized. From 12 weeks of ovariectomy, mice were administered BPX (600 mg/kg) mixed in a chow diet for 20 weeks. Changes in bone mineral density (BMD) and bone volume (BV), histological findings, osteogenic markers in serum, and bone formation-related molecules were analyzed. Ovariectomy notably decreased the BMD and BV scores, while these were significantly attenuated by BPX treatment in the whole body, femur, and tibia. These anti-osteoporosis effects of BPX were supported by the histological findings for bone microstructure from H&E staining, increased activity of alkaline phosphatase (ALP), but a lowered activity of tartrate-resistant acid phosphatase (TRAP) in the femur, along with other parameters in the serum, including TRAP, calcium (Ca), osteocalcin (OC), and ALP. These pharmacological actions of BPX were explained by the regulation of key molecules in the bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) pathways. The present results provide experimental evidence for the clinical relevance and pharmaceutical potential of BPX as a candidate for anti-osteoporosis treatment, especially under postmenopausal conditions.

The pathophysiology of nonalcoholic steatohepatitis (NASH) is complex, owing to its diverse pathological drivers and, until recently, there were no approved drugs for this disease. Tecomella is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. The administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in western diet sugar water (WDSW) fed mice but had no effect on chow diet normal water (CDNW) fed mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced Endoplasmic Reticulum stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were comparable to saroglitazar, the approved drug used to treat human NASH and the positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH.

Pyroptosis is an active and ordered form of programmed cell death. The signaling pathways of pyroptosis are mainly divided into canonical pathways mediated by caspase-1 and noncanonical pathways mediated by caspase-11. Cell pyroptosis is characterized by the activation of inflammatory caspases (mainly caspase-1, 4, 5, 11) and cleavage of various members of the Gasdermin family to form membrane perforation components, leading to cell membrane rupture, inflammatory mediators release, and cell death. Moderate pyroptosis is an innate immune response that fights against infection and plays an important role in the occurrence and development of the normal function of the immune system. However, excessive pyroptosis occurs and leads to immune disorders in many pathological conditions. Based on canonical pathways, research on pyroptosis regulation has demonstrated several pyroptotic inhibitors, including small-molecule drugs, natural products, and formulations of traditional Chinese medicines. In this paper, we review the characteristics and molecular mechanisms of pyroptosis, summarize inhibitors of pyroptosis, and propound that herbal medicines should be a focus on the research and development for pyroptosis blockers.

Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.

Esophageal cancer (EC) is one of the most malignant types of cancer worldwide and has a high incidence and mortality rate in Asian countries. When it comes to treating EC, although primary methods such as chemotherapy and surgery exist, the prognosis remains poor. The purpose of this current research is to review the range of effects that natural products have on cancer by analyzing studies conducted on EC. Fifty-seven studies were categorized into four anti-cancer mechanisms, as well as clinical trials. The studies that were scrutinized in this research were all reported within five years. The majority of the substances reviewed induced apoptosis in EC, acting on a variety of mechanisms. Taken together, this study supports the fact that natural products have the potential to act as a candidate for treating EC.

Nasal mucosa injury can be caused by trauma, radiotherapy, chronic infection such as sinusitis, and post sinus surgery. The rate of healing and its treatment are important in the recovery of patients especially in post sinus surgery, which introduces new injuries. In this review, the current knowledge in terms of the mechanism underlying nasal wound healing was initially discussed. The currently available treatment options for enhancement of wound healing following sinus surgery were discussed and these had included intravenous antibiotics or steroids, various nasal sprays, and nasal packing. In addition, emerging alternative therapies in nasal mucosa wound healing such as herbal medicine and the advancement of regenerative medicine therapies such as stem cells and their byproducts were also discussed. Despite the various available treatment options for wound healing in nasal mucosa, rigorous strong evidence of their efficacy is gravely warranted in order to recommend them as part of the treatment modality. [ABSTRACT FROM AUTHOR]