The anti-hyperplasia effect of polysaccharide from Prunella vulgaris L. on mammary gland hyperplasia in rats through regulation of the AKT-FOXO3a signaling pathway and intestinal flora.

BACKGROUND: Prunella vulgaris L., a medicinal and edible homologous plant, is often used to treat conditions such as breast hyperplasia, thyroid enlargement and lymphatic tuberculosis. Research has demonstrated that it is particularly effective in the treatment of mammary gland hyperplasia (MGH). However, the material basis and mechanism of its efficacy are still unclear. RESULTS: Our results showed that in rats with MGH, polysaccharide from Prunella vulgaris L. (PVP) led to a reduction in the levels of estradiol, prolactin and malondialdehyde, while simultaneously increasing the concentrations of progesterone (P), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD) and catalase (CAT) in the serum. In addition, results obtained from 16S rRNA sequencing demonstrated that PVP had the capacity to increase the richness and diversity of the intestinal microbiota in MGH rats, as well as modify the structure of the microbiota. Correlation analysis revealed that the levels of P, SOD, MnSOD and CAT were positively associated with Allobaculum, Romboutsia, Faecalibaculum and Clostridium, while negatively correlated with Turicibacter. CONCLUSIONS: The mechanism of PVP in treating MGH might be through inhibiting the phosphorylation of the AKT-FOXO3a signaling pathway and then activating the expression of downstream antioxidant enzymes, such as MnSOD and CAT. At the same time, PVP could restore intestinal flora homeostasis in rats with MGH by regulating the flora changes of Allobaculum, Romboutsia, Clostridium and Faecalibaculum, thereby reducing oxidative stress in rats with MGH. © 2024 Society of Chemical Industry.

Mechanism of Prunella vulgaris L. and luteolin in restoring Tfh/Tfr balance and alleviating oxidative stress in Graves' disease.

BACKGROUND: The pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PURPOSE: This study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). METHODS: High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. RESULTS: A total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. CONCLUSION: XKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.

Effect and mechanism of Prunella vulgaris L. extract on alleviating lipopolysaccharide-induced acute mastitis in protecting the blood-milk barrier and reducing inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: According to ancient literature, Prunella vulgaris L. (P vulgaris) alleviates mastitis and has been used in China for many years; however, there are no relevant reports that confirm this or the mechanism of its efficacy. AIM OF THE STUDY: To explore the anti-acute mastitis effect and potential mechanism of P vulgaris extract. MATERIALS AND METHODS: First, the active ingredients and targets of P vulgaris against mastitis were predicted using network pharmacology. Next, the relevant active ingredients were enriched using macroporous resins and verified using UV and UPLC-Q-TOF-MS/MS. Lastly, a mouse model of acute mastitis was established by injecting lipopolysaccharides into the mammary gland and administering P vulgaris extract by oral gavage. The pathological changes in mammary tissue were observed by HE staining. Serum and tissue inflammatory factors were measured by ELISA method. MPO activity in mammary tissue was measured using colorimetry and MPO expression was detected by immunohistochemistry. The expression of tight junction proteins (ZO-1, claudin-3, and occludin) in mammary tissue was detected by immunofluorescence and Western blot. iNOS and COX-2 in mammary tissue were detected by Western blot. MAPK pathway and NF-κB pathway related proteins were also detected by Western blot. RESULTS: Network pharmacology predicted that phenolic acids and flavonoids in P vulgaris had anti-mastitis effects. The contents of total flavonoids and total phenolic acids in P vulgaris extract were 64.5% and 29.4%, respectively. UPLC-Q-TOF-MS/MS confirmed that P vulgaris extract contained phenolic acids and flavonoids. The results of animal experiments showed that P vulgaris extract reduced lipopolysaccharide-induced inflammatory edema, inflammatory cell infiltration, and interstitial congestion of mammary tissue. It also reduced the levels of serum and tissue inflammatory factors TNF-α, IL-6, and IL-1ß, and inhibited the activation of MPO. Furthermore, it downregulated the expression of MAPK and NF-κB pathway-related proteins. The expressions of ZO-1, occludin, and claudin-3 in mammary gland tissues were upregulated. CONCLUSIONS: P vulgaris extract can maintain the integrity of mammary connective tissue and reduce its inflammatory response to prevent acute mastitis. Its mechanism probably involves regulating NF-κB and MAPK pathways.

Exploring the Antibacterial Potential and Underlying Mechanisms of Prunella vulgaris L. on Methicillin-Resistant Staphylococcus aureus.

Prunella vulgaris L. (PV) is a widely distributed plant species, known for its versatile applications in both traditional and contemporary medicine, as well as in functional food development. Despite its broad-spectrum antimicrobial utility, the specific mechanism of antibacterial action remains elusive. To fill this knowledge gap, the present study investigated the antibacterial properties of PV extracts against methicillin-resistant Staphylococcus aureus (MRSA) and assessed their mechanistic impact on bacterial cells and cellular functions. The aqueous extract of PV demonstrated greater anti-MRSA activity compared to the ethanolic and methanolic extracts. UPLC-ESI-MS/MS tentatively identified 28 phytochemical components in the aqueous extract of PV. Exposure to an aqueous extract at ½ MIC and MIC for 5 h resulted in a significant release of intracellular nucleic acid (up to 6-fold) and protein (up to 10-fold) into the extracellular environment. Additionally, this treatment caused a notable decline in the activity of several crucial enzymes, including a 41.51% reduction in alkaline phosphatase (AKP), a 45.71% decrease in adenosine triphosphatase (ATPase), and a 48.99% drop in superoxide dismutase (SOD). Furthermore, there was a decrease of 24.17% at ½ MIC and 27.17% at MIC in tricarboxylic acid (TCA) cycle activity and energy transfer. Collectively, these findings indicate that the anti-MRSA properties of PV may stem from its ability to disrupt membrane and cell wall integrity, interfere with enzymatic activity, and impede bacterial cell metabolism and the transmission of information and energy that is essential for bacterial growth, ultimately resulting in bacterial apoptosis. The diverse range of characteristics exhibited by PV positions it as a promising antimicrobial agent with broad applications for enhancing health and improving food safety and quality.

Exploring the mechanism of bioactive components of Prunella vulgaris L. in treating hepatocellular carcinoma based on network pharmacology.

In traditional Chinese Medicine, Prunella vulgaris L. (PVL) is potentially effective in the treatment of some human malignancies including hepatocellular carcinoma (HCC). However, the detailed mechanism of action remains unclear. The purpose of this study was to decipher the constitutes of the bioactive ingredients of PVL, and its mechanism against HCC using network pharmacology and in vitro experiments. The bioactive components of PVL were obtained by Traditional Chinese Medicine System Pharmacology Database and Analysis platform database, and the targets of bioactive components of PVL was investigated by Swiss Target Prediction database. HCC related targets were obtained from GEO database, GeneCards database and DisGeNET database, and the gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted for annotating the biological function of gene targets. A protein-protein interaction network was constructed using STRING database. Molecular docking of key bioactive ingredients was performed using AutoDock Vina. Cell proliferation and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. The expression level of the target genes of PI3K/Akt pathway were detected by qPCR. In the present work, 11 bioactive components of PVL were screened out, which acted on 177 potential targets. In addition, 13,517 genes were strongly associated with HCC pathogenesis, of which 158 targets are overlapped with PVL's targets. KEGG results identified 39 signaling pathways closely associated with the 158 targets. Molecular docking showed that the main bioactive components of PVL, kaempferol, morin, quercetin, luteolin, and spinasterol, had good binding activity with the core proteins in cancer biology such as AKT1, EGFR, SRC, ESR1, and PPARG. In vitro assays showed that quercetin, one of the main components of PVL extracts effectively inhibited HCC cell proliferation, and promoted apoptosis, which may be associated with PI3K/AKT signaling pathway. In summary, PVL may regulate HCC progression by regulating core targets such as AKT1, EGFR, SRC, ESR1, and PPARG, and acting on PI3K-Akt signaling pathway.

Prunella vulgaris L.: An Updated Overview of Botany, Chemical Composition, Extraction Methods, and Biological Activities.

Prunella vulgaris L. (PV) is a well-known renewable drug resource full of different groups of biologically active substances with a wide range of pharmacological actions and applications in medicine. In this review, we present an updated comprehensive overview of the botany, extracting methods, chemical composition, and pharmacological activity of different parts of PV extracts. As a result of this review, it was found that chemical composition of PV depends on various factors ranging from the part of the plant to the method of extraction. We also highlight extraction methods that have not been previously used for obtaining PV extracts and may have high scientific interest. With this review, we hope to guide present and future professionals and provide possible previously unexplored areas to find new solutions associated with PV plant.

An aqueous extract of Prunella vulgaris L. ameliorates cadmium-induced bone loss by promoting osteogenic differentiation in female rats.

Cadmium (Cd) causes bone loss, concerning inhibiting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Prunella vulgaris L. (PV) has the potential for promoting osteogenic differentiation, but its influence on Cd-induced bone loss is unclear. This study investigated the effect of PV aqueous extract (PVE) on Cd-induced bone loss and its underlying mechanisms. Eight-week-old female SD rats were randomly assigned into four groups and treated for 16 weeks: Control, Cd (50 mg/L of Cd chloride), Cd + PV Low (125 mg/kg bw of PVE), and Cd + PV High (250 mg/kg bw of PVE). PV ameliorated femoral bone loss in Cd-treated rats manifested as increases in bone mineral density, bone volume, trabecular thickness, number, and area, and decreases in trabecular separation. Compared with Cd group, PV-treatment groups had higher serum levels of bone formation markers (ALP, BGP). Additionally, in PV-treatment groups, expressions of bone formation markers (Osterix, Runx2) and molecules involved in osteogenic differentiation signal pathway BMP/Smad (BMP4, Smad1/5/9) in the tibia of rats and isolated rat primary BMSCs were upregulated. These results suggest that PV alleviates Cd-induced bone loss by promoting osteogenic differentiation, which is likely associated with BMP/Smad pathway.

Exogenous Melatonin Enhances the Yield and Secondary Metabolite Contents of Prunella vulgaris by Modulating Antioxidant System, Root Architecture and Photosynthetic Capacity.

Melatonin (MT) plays a number of key roles in regulating plant growth and secondary metabolite accumulation. Prunella vulgaris is an important traditional Chinese herbal medicinal plant which is used for the treatment of lymph, goiter, and mastitis. However, the effect of MT on the yield and medicinal component content of P. vulgaris remains still unclear. In this research, we have examined the influence of different concentrations of MT (0, 50, 100, 200, 400 µM) on the physiological characteristics, secondary metabolite contents, and yield of P. vulgaris biomass. The results showed that 50-200 µM MT treatment had a positive effect on P. vulgaris. MT treatment at 100 µM greatly increased the activities of superoxide dismutase and peroxidase, the contents of soluble sugar and proline, and obviously decreased the relative electrical conductivity, the contents of malondialdehyde and hydrogen peroxide of leaves. Furthermore, it markedly promoted the growth and development of the root system, increased the content of photosynthetic pigments, improved the performance of photosystems I and II and the coordination of both photosystems, and enhanced the photosynthetic capacity of P. vulgaris. In addition, it significantly increased the dry mass of whole plant and spica and promoted the accumulation of total flavonoids, total phenolics, caffeic acid, ferulic acid, rosmarinic acid, and hyperoside in the spica of P. vulgaris. These findings demonstrated that the application of MT could effectively activate the antioxidant defense system of P. vulgaris, protect the photosynthetic apparatus from photooxidation damage, and improve the photosynthetic capacity and the root absorption capacity, thereby promoting the yield and accumulation of secondary metabolites in P. vulgaris.

Pentacyclic triterpenoids from spikes of Prunella vulgaris L. with thyroid tumour cell cytostatic bioactivities.

Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.

An in vivo and in vitro assessment of the anti-breast cancer activity of crude extract and fractions from Prunella vulgaris L.

Prunella vulgaris L.(P. vulgaris) is a perennial herb belonging to the Labiate family and widely distributed in China, Japan, Korea and Europe. Medical monographs and previous studies have shown that P. vulgaris has significant anti-breast cancer activity, and its use in breast treatment has a long history. However, systematically reports about the material basis and mechanism of P. vulgaris on anti-breast cancer activity are limited. In the present study, we first screened the best active fraction from the crude extract (PVE) and ethanol eluted fractions of P. vulgaris by using MDA-MB-231, MCF-7, 4T1 cell models in vitro and a 4T1-BALB/c transplanted tumour mouse breast cancer model in vivo. Furthermore, the anti-breast cancer mechanism of the best active fraction was investigated. The results demonstrated that PVE and ethanol fractions exhibited anti-breast cancer activity, especially with the 50% ethanol eluted fraction (PV50), which effectively regulated the 4T1 cell cycle, inhibited tumour cell proliferation, and promoted cancer cell apoptosis. In case of in vivo assays, PV50 inhibited tumour growth and lung metastasis, as well as inducing cell apoptosis by promoting damage of nuclear DNA and increasing expression of cleaved caspase-3. In addition, the chemical compositions of PV50 were analyzed by HPLC and UPLC-MS/MS, which were identified as flavonoids, moderately polar triterpenes, and a small amount of phenolic acid. The PV50 could be applied as natural sources against breast cancer in the pharmaceutical industry. These findings provide a basis for understanding the mechanism of the anti-breast cancer activity of P. vulgaris.

Systematic Identification and Validation of Suitable Reference Genes for the Normalization of Gene Expression in Prunella vulgaris under Different Organs and Spike Development Stages.

The quantitative real-time PCR (qRT-PCR) is an efficient and sensitive method for determining gene expression levels, but the accuracy of the results substantially depends on the stability of the reference gene (RG). Therefore, choosing an appropriate reference gene is a critical step in normalizing qRT-PCR data. Prunella vulgaris L. is a traditional Chinese medicine herb widely used in China. Its main medicinal part is the fruiting spike which is termed Spica Prunellae. However, thus far, few studies have been conducted on the mechanism of Spica Prunellae development. Meanwhile, no reliable RGs have been reported in P. vulgaris. The expression levels of 14 candidate RGs were analyzed in this study in various organs and at different stages of Spica Prunellae development. Four statistical algorithms (Delta Ct, BestKeeper, NormFinder, and geNorm) were utilized to identify the RGs' stability, and an integrated stability rating was generated via the RefFinder website online. The final ranking results revealed that eIF-2 was the most stable RG, whereas VAB2 was the least suitable as an RG. Furthermore, eIF-2 + Histon3.3 was identified as the best RG combination in different periods and the total samples. Finally, the expressions of the PvTAT and Pv4CL2 genes related to the regulation of rosmarinic acid synthesis in different organs were used to verify the stable and unstable RGs. The stable RGs in P. vulgaris were originally identified and verified in this work. This achievement provides strong support for obtaining a reliable qPCR analysis and lays the foundation for in-depth research on the developmental mechanism of Spica Prunellae.

Integrative transcriptomic, proteomic and metabolomic analysis reveals the dynamic regulation of secondary metabolism upon development of Prunella vulgaris L.

Prunella vulgaris L. (P. vulgaris, Labiatae) is a perennial medicinal and edible plant widely used in China, Korea, Japan and Europe. The reddish brown spica of P. vulgaris (Prunellae Spica), which is collected in summer, has been commonly used in traditional medicine and food industry, while it is also used with whole grass in Europe and Taiwan. To clarify the regulatory pathways and mechanism of quality formation in P. vulgaris, targeted metabolomic, transcriptomic, and proteomic analyses of Prunellae Spica samples from five consecutive developmental stages were carried out. The results showed that terpenoids were mainly synthesized in the maturity stage of Prunellae Spica, with the key enzymes and coding genes in downstream pathways being mainly expressed during ripening, while related enzymes in the upstream pathway showed the opposite pattern. Flavonoids mainly accumulated before ripening, with highly expressed pathway enzymes and coding genes. The accumulation of phenylpropanoids was relatively active throughout the development process. Rosmarinic acid (RA) and its synthetic intermediate products mainly accumulated via more active pathway enzymes and coding genes before ripening. The regulatory factors and metabolites related to RA synthesis were mainly enriched in phenylpropanoid biosynthesis, plant hormone signal transduction, plant pathogen interaction, oxidative phosphorylation, and endoplasmic reticulum protein processing pathways.

Emerging therapeutic role of Prunella vulgaris in thyroid disease.

Thyroid disease is characterized by unusual levels of thyroid hormones, which results in either hyperthyroidism or hypothyroidism. The pathology of a particular type or stage of thyroid disease is very complicated, and always linked to a variety of biological functions. Although the mortality rate is not high, thyroid dysfunction could lead to metabolic and immunological disorders that can subsequently cause discomfort. To date, many drugs are suggested to have curative effects on thyroid disease, however, drug toxicity and long treatment periods encourage the search for more promising ones. Prunella vulgaris L. (Labiatae) is a popular herb that has shown great potential for improving human immunity and organ protection. It has been extensively used in the treatment of many diseases but its ability to treat specific diseases has not been fully reported. In this review, a literature search regarding herbs and herbal recipes for treating thyroid disease were carried out, organized, and summarized. In addition, this study conducted a literature search on the current situation and progress of P. vulgaris treatment for various diseases. Finally, this study discussed studies regarding P. vulgaris treatment of goiter, and the mechanism of treatment through the regulation of apoptosis. Accordingly, a combination therapy of herbs and Western medicine can provide significant therapeutic effects in the clinical treatment of thyroid disease. Furthermore, the association between P. vulgaris and various diseases suggests that P. vulgaris is rich in a variety of active substances that can fight oxidation and participate in the regulation of apoptosis, thus having a protective effect on the thyroid. Here, a comprehensive literature review regarding the application of herbs or herbal recipes in the treatment of thyroid disease was presented. It is concluded that there is strong evidence for further research regarding the use of P. vulgaris in the treatment of thyroid diseases.

Phytochemistry, Pharmacology and Quality Control of Xiasangju: A Traditional Chinese Medicine Formula.

As a traditional Chinese herbal formula, Xiasangju (XSJ) is widely used in China for antipyresis and influenza treatment. However, XSJ still fails to have a comprehensive summary of the research progress in the last decade. This review summarizes the advanced research on the extraction process, phytochemistry, pharmacological activity, and quality control of XSJ. Current research mainly focuses on quality control and the pharmacological effects of single herbs and active ingredients, but many pharmacological mechanisms of the formula are unclear. The development of active ingredients reflects the active characteristics of triterpenes, phenolic acids and flavonoids, but the hepatotoxicity of Prunella vulgaris L. has not been taken into account. XSJ has extensive historical practical experiences, while systematic clinical trials remain lacking. Therefore, it is necessary to study the active ingredients and define the mechanisms of XSJ to develop multiple applications, and further studies on the dose range between its hepatoprotective activity and hepatotoxicity are necessary to improve the safety of the clinical application. In this review, the current problems are discussed to facilitate the reference basis for the subsequent research on the development of XSJ and future application directions.

Prunella vulgaris L. - A Review of its Ethnopharmacology, Phytochemistry, Quality Control and Pharmacological Effects.

Prunella vulgaris L. (PVL) is dried fruit spike of Lamiacea plant Prunella vulgaris L., which is a perennial herb with medicinal and edible homology used for thousands of years. PVL is bitter, acrid, cold, and belongs to the liver and gallbladder meridians. It clears the liver and dissipate fire, improve vision, disperse swelling, and has satisfactory clinical therapeutic effects on many diseases such as photophobia, dizziness, scrofula, goiter, breast cancer. The collection of information and data related to PVL comes from literatures retrieved and collated from various online scientific databases (such as CNKI, VIP, PubMed, Web of Science, Research Gate, Science Database), ancient books of traditional chinese medicine (Encyclopedia of Traditional Chinese Medicine, Classics of Traditional Chinese Medicine, Dictionary of Traditional Chinese Medicine), and Doctoral and Master's Dissertations. Currently, the major chemical constituents isolated and identified from PVL are triterpenoids, steroids, flavonoids, phenylpropanoids, organic acids, volatile oils and polysaccharides. Modern pharmacological studies have shown that PVL has a wide range of pharmacological activities, including anti-inflammatory, anti-tumor, antibacterial and antiviral effects, as well as immune regulation, antihypertensive, hypoglycemic, lipid-lowering, antioxidant, free radical scavenging, liver protection, sedative and hypnotic effects. This paper reviewes the botany, ethnopharmacology, traditional application, phytochemistry, analytical methods, quality control, pharmacological effects of PVL. It can be used not only as medicine, but also gradually integrated into the "medicine and food homology" and "Chinese medicine health" boom. More importantly, it has great potential for drug resources development. This paper deeply discusses the shortcomings of current PVL research, and proposes corresponding solutions, in order to find a breakthrough point for PVL research in the future. At the same time, it is necessary to further strengthen the research on its medicinal chemistry, mechanism of action and clinical application efficacy in the future, and strive to extract, purify and synthesize effective components with high efficiency and low toxicity, so as to improve the safety and rationality of clinical medication.

Emerging therapeutic role of Prunella vulgaris in thyroid disease / 中草药·英文版

Thyroid disease is characterized by unusual levels of thyroid hormones, which results in either hyperthyroidism or hypothyroidism. The pathology of a particular type or stage of thyroid disease is very complicated, and always linked to a variety of biological functions. Although the mortality rate is not high, thyroid dysfunction could lead to metabolic and immunological disorders that can subsequently cause discomfort. To date, many drugs are suggested to have curative effects on thyroid disease, however, drug toxicity and long treatment periods encourage the search for more promising ones. Prunella vulgaris L. (Labiatae) is a popular herb that has shown great potential for improving human immunity and organ protection. It has been extensively used in the treatment of many diseases but its ability to treat specific diseases has not been fully reported. In this review, a literature search regarding herbs and herbal recipes for treating thyroid disease were carried out, organized, and summarized. In addition, this study conducted a literature search on the current situation and progress of P. vulgaris treatment for various diseases. Finally, this study discussed studies regarding P. vulgaris treatment of goiter, and the mechanism of treatment through the regulation of apoptosis. Accordingly, a combination therapy of herbs and Western medicine can provide significant therapeutic effects in the clinical treatment of thyroid disease. Furthermore, the association between P. vulgaris and various diseases suggests that P. vulgaris is rich in a variety of active substances that can fight oxidation and participate in the regulation of apoptosis, thus having a protective effect on the thyroid. Here, a comprehensive literature review regarding the application of herbs or herbal recipes in the treatment of thyroid disease was presented. It is concluded that there is strong evidence for further research regarding the use of P. vulgaris in the treatment of thyroid diseases.

Prunella vulgaris L. Attenuates Experimental Autoimmune Thyroiditis by Inhibiting HMGB1/TLR9 Signaling.

BACKGROUND: Prunella vulgaris L. (PV) has been used to treat autoimmune thyroiditis (AIT), but the underlying mechanism remains unknown. The present study was designed to evaluate the effect of PV on AIT and explore the role of high-mobility group box-1 (HMGB1) signaling in PV-mediated effects in vivo and in vitro. METHODS: In the present study, bioactive components of PV were identified using UPLC-ESI-MS. The protective effects and potential mechanisms critical for the anti-inflammatory and immunomodulatory effects of PV in AIT were investigated in a rat model of thyroglobulin-induced experimental autoimmune thyroiditis (EAT) and in lipopolysaccharide (LPS)-induced thyroid follicular cells (TFCs). RESULTS: The main bioactive compound identified in PV was rosmarinic acid. The thyroid volume, thyroiditis inflammation score and serum thyroglobulin antibody levels of EAT rats were attenuated by PV treatment (P<0.01). In addition, PV significantly reduced the elevated levels of the proinflammatory cytokines TNF-α, IL-6, IL-1ß and monocyte chemoattractant protein-1 (MCP-1) both in vivo (P<0.01) and in vitro (P<0.05). PV downregulated HMGB1 mRNA and protein expression, reduced HMGB1 secretion, and inhibited TLR9 signaling pathways (TLR9 and MyD88) in PV-treated EAT rats and TFCs. Moreover, PV reversed the increases in the numbers of splenic Th1, Th2, and Th17 cells. Finally, our results acquired following administration of ethyl pyruvate, an HMGB1 inhibitor, to splenocytes cultured in vitro supported the hypothesis that the HMGB1/TLR9 pathway is involved in the PV-mediated reductions in Th1, Th2 and Th17 cells. CONCLUSION: PV decreased the activity of the TLR9/MyD88 pathway and proinflammatory cytokines through HMGB1. In addition, we are the first to show that PV attenuated the HMGB1-induced increases in Th1, Th2 and Th17 cells in AIT models. These findings provide new evidence for the potential therapeutic value of PV as a treatment for AIT and other autoimmune diseases.

Screening out the anti-insomnia components from Prunella vulgaris L. based on plasma pharmacochemistry combined with pharmacodynamic experiments and UPLC-MS/MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. AIMS OF THIS REVIEW: P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. MATERIALS AND METHODS: In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulgaris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. RESULTS: It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris, which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. CONCLUSIONS: This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris.

An aqueous extract of Prunella vulgaris L. inhibits the growth of papillary thyroid carcinoma by inducing autophagy in vivo and in vitro.

The continued global rise in papillary thyroid carcinoma (PTC) combined with potential adverse effects of regular treatments calls for an alternative therapy. Prunella vulgaris L. (PV) is commonly used as a herbal remedy for thyroid diseases in China, but its influence on PTC is unclear. This study investigated the effect of PV aqueous extract on PTC and its underlying mechanism using a mouse xenograft model and the human PTC cell line K1. PV suppressed tumor growth in PTC-bearing mice at 0.05 and 0.1 g/kg bw, accompanied by improvements in autophagy-related protein expressions in xenografts. In K1 cells, PV inhibited cell growth and induced autophagic flux, manifesting as changes in autophagy-related proteins, the presence of autophagosomes, and a further increase in LC3-II by co-incubation with bafilomycin A1. Autophagy inhibitor 3-methyladenine ameliorated the autophagic cell death caused by PV. The mammalian target of rapamycin (mTOR) activator MHY1485 blocked the antiproliferative activity of PV by regulating mTOR, unc-51-like autophagy activating kinase 1 (ULK1), autophagosomes formation, and autophagy-related proteins. The adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C attenuated PV-induced inhibition of mTOR. Our results suggest that PV inhibits the growth of PTC in vivo and in vitro via autophagy, which is associated with the AMPK/mTOR/ULK1 pathway. Thus, PV has the potential to function as a therapeutic agent against PTC.

Comparative proteomic analysis of Prunella vulgaris L. spica ripening.

Prunella vulgaris L., better known as 'self-heal', has been extensively used in the traditional system of medicines. To reveal the regulatory mechanism of its development, TMT-based quantitative proteome analysis was performed in the Prunella vulgaris L. spica before and during ripening (Group A and Group B, respectively). This analysis resulted in the identification of 7655 proteins, of which 1910 showed differential abundance between the two groups. Pronounced changes in the proteomic profile included the following: 1) Stress-responsive proteins involved in protecting cells and promoting fruit ripening and seed development were highly abundant during ripening. 2) The degradation of chlorophyll, inhibition of chlorophyll biosynthesis and increased abundance of transketolase occurred simultaneously in the spica of Prunella vulgaris L., resulting in the spica changing color from green to brownish red. 3) The abundance of protein species related to phenylpropanoid biosynthesis mainly increased during ripening, while flavonoid and terpenoid backbone biosynthesis mostly occurred before ripening. SIGNIFICANCE: This study establishes a link between protein profiles and mature phenotypes, which will help to improve our understanding of the molecular mechanisms involved in the maturation of Prunella vulgaris L. at the proteome level and reveal the scientific connotation for the best time to harvest Prunella vulgaris L. This work provides a scientific basis for the production of high-quality medicinal Prunella vulgaris L., as well as a typical demonstration of molecular research used for the harvest period of traditional Chinese medicine. BIOLOGICAL SIGNIFICANCE: This work provided a comprehensive overview on the functional protein profile changes of Prunella vulgaris L. spica at different growing stages, as well as the scientific rationale of Prunella vulgaris L. harvested in summer after brownish red, thus laid an intriguing stepping stone for elucidating the molecular mechanisms of quality development.