Selfheal (Prunella vulgaris) and Immune support: evidence and sources

Objective Enhancing innate immunity through interferons (IFNs) and IFN-stimulated genes (ISGs) offers a promising strategy for preventing herpes simplex virus type 1 (HSV-1) infection. Prunella vulgaris L., a medicinal herb, has demonstrated significant anti-HSV activity; in particular, its derived polysaccharide complex (PVE30) effectively inhibits viral replication. In this study, we investigate whether PVE30 exerts an anti-HSV-1 activity through activation of the innate immune response. Methods To determine the primary stage at which PVE30 exerts its effects during the HSV-1 life cycle, plaque reduction assays were conducted. Viral infection was further assessed by investigating the DNA copies, mRNA levels and protein expression of HSV-1 in infected cells using real-time polymerase chain reaction (RT-PCR) and Western blotting. The activation of the innate immune response was evaluated by detecting mRNA levels of ISGs, including MX dynamin-like GTPase 1 (Mx1), Mx2, 2'-5'-oligoadenylate synthetase 1 (OAS1), ISG15 and IFN regulatory factor 7 (IRF7) using RT-PCR, and levels of TANK-binding kinase 1 (TBK1) and IRF3 proteins using Western blotting. The translocation of phosphorylated IRF3 and stimulator of IFN genes (STING) was observed through fluorescence microscopy. Results PVE30 pre-treatment exerted protective effects against HSV-1 infection in human immortalized keratinocytes by enhancing the innate immune response. This was shown by increased transcriptional levels of IFN-β and antiviral ISGs, along with a significant reduction in HSV-1 DNA copies, mRNA expression and protein levels. Mechanistically, PVE30 promoted TBK1 phosphorylation, leading to nuclear translocation of IRF3 and subsequent IFN-β transcription; these effects were diminished by TBK1 inhibitor GSK8612. Additionally, STING was identified as a key mediator in PVE30-activated TBK1 signaling, as its inhibition induced by C-176 reduced PVE30's efficacy. Conclusion This study elucidated the molecular mechanisms underlying the protective effects of PVE30 against HSV-1 infection. PVE30 exerted its protective role by enhancing STING-TBK1-IRF3 pathway-mediated innate immune response. Please cite this article as: Zhang YB, Xu L, Yuan M, Liu MF, Li Y, Zhong XL, Lin ZX, Xian YF, Lu P, Xi ZC, Xu HX. Protective effects of Prunella vulgaris polysaccharides against herpes simplex virus type 1 infection through the STING-TBK1-IRF3 pathway. J Integr Med. 2026; 24(3):454-465.

Background Prunella vulgaris polysaccharide extracted by hot water and 30% ethanol precipitation (PVE30) was reported to possess potent antiviral effects against herpes simplex virus (HSV) infection. However, its anti-HSV mechanism has not yet been fully elucidated. Purpose This study aimed to investigate the potential mechanisms of PVE30 against HSV infection. Methods Antiviral activity was evaluated by a plaque reduction assay, and the EC 50 value was calculated. Immunofluorescence staining and heparin bead pull-down assays confirmed the interactions between PVE30 and viral glycoproteins. Real-time PCR was conducted to determine the mRNA levels of viral genes, including UL54, UL29, UL27, UL44, and US6, and the proinflammatory cytokines IL-6 and TNF-α. The protein expression of viral proteins (ICP27, ICP8, gB, gC, and gD), the activity of the TLR-NF-κB signalling pathway, and necroptotic-associated proteins were evaluated by Western blotting. The proportion of necroptotic cells was determined by flow cytometric analysis. Results The P. vulgaris polysaccharide PVE30 was shown to compete with heparan sulfate for interaction with HSV surface glycoprotein B and gC, thus strongly inhibiting HSV attachment to cells. In addition, PVE30 downregulated the expression of IE genes, which subsequently downregulated the expression of E and L viral gene products, and thus effectively restricted the yield of progeny virus. Further investigation confirmed that PVE30 inhibited TLR2 and TLR3 signalling, leading to the effective suppression of NF-κB activation and IL-6 and TNF-α expression levels, and blocked HSV-1-induced necroptosis by reducing HSV-1-induced phosphorylation of MLKL. Conclusion Our results demonstrate that the P. vulgaris polysaccharide PVE30 is a potent anti-HSV agent that blocks TLR-mediated NF-κB activation.

The herbhas shown significant immune-stimulatory and anti-inflammatory effects in mouse models. Here, the effects of a novel-containing herbal mixture, PV-1, were examined in several mouse models for cancer, including chemically induced models of lung and oral cancers as well as syngraft models for lung cancer and melanoma. PV-1, consisting of extracts from,,and, exhibited no toxicity in a dose escalation study in A/J mice. PV-1 significantly inhibited mouse lung tumor development induced by the lung carcinogens vinyl carbamate and benzo[a]pyrene. PV-1 also hindered the induction of oral squamous cell carcinomas in C57BL/6 mice caused by 4-nitroquinoline-1-oxide. Flow cytometry analysis showed that PV-1 increased the numbers of CD8+ tumor-infiltrating lymphocytes (TILs) and increased the production of granzyme B, TNF-α, and IFN-γ by CD8+ TILs. PV-1 also suppressed granulocytic myeloid-derived suppressor cell numbers (g-MDSCs) and improved the anti-cancer activity of anti-PD-1 immunotherapy. These results indicate that PV-1 remodels the tumor immune microenvironment by selectively inhibiting g-MDSCs and increasing CD8+ TILs within tumors, resulting in decreased immune suppression and enhanced cancer chemopreventive efficacy.

Autoimmune thyroiditis (AIT), one of the most common autoimmune diseases among women of reproductive age, is closely associated with reproductive failure and other obstetric complications. However, effective clinical strategies for the management of pregnant women with AIT are limited. It has been shown that Prunella vulgaris (PV), a traditional herbal medicine, can ameliorate AIT and other common thyroid disorders. Therefore, using an experimental autoimmune thyroiditis (EAT) rat model, we investigated the potential effects of PV on AIT-related pregnancy outcomes. According to the administered dose of PV, EAT rats were randomly divided into the untreated EAT and PV-treated EAT groups. We found that thyroid peroxidase antibody and thyroglobulin antibody serum levels and the inflammatory infiltration of the thyroid were reduced in all PV-treated groups. Increased splenic Tgfb1 mRNA levels and Treg cell proportions were associated with decreased Th1/Th17 cell proportions, and Ifng mRNA levels were reduced in rats that received low and medium doses of PV. Moreover, in the low-dose PV group, fetal development retardation and placental injuries were reversed. Overall, our findings indicated that PV could alleviate AIT and improve pregnancy outcomes in EAT rats by downregulating Th1/Th17 immune responses and inducing Treg cell proliferation.

Aim To investigate the ability of a Prunella vulgaris (P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a(-/-) mice. Methods Vehicle (5% ethanol) or P. vulgaris ethanolic extract (2.4 mg/d) were administered daily by oral gavage to mdr1a(-/-) or wild type FVB(WT) mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencing weight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. Results Administration of P. vulgaris extracts to mdr1a(-/-) mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a(-/-) mice. Oral administration of the P. vulgaris extract resulted in reduced (P Conclusion The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a(-/-) mice.

The organic fraction (OF; 25.7% w/w of rosmarinic acid) of Prunella vulgaris (total extract) was found to exhibit the following: scavenging activity on diphenylpicrylhydrazyl radical (DPPH), inhibition of in vitro human LDL Cu(II)-mediated oxidation, protection of rat mitochondria and rat hepatocytes exposed to either tert-butyl hydroperoxide, or to Cu(II) and Fe(III) ions. OF also showed a potential to inhibit rat erythrocyte haemolysis and it reduced the production of LTB(4) in bovine PMNL generated by the 5-lipoxygenase pathway. Other observations included antiproliferative effects against HaCaT cells and mouse epidermal fibroblasts and a moderate OF antimicrobial activity on gram-positive bacteria. Rosmarinic, caffeic and 3-(3,4-dihydroxyphenyl)lactic acids exhibited less potent activity than the plant extract in all bioassays. The antioxidative, antimicrobial, together with antiviral effects offer good prospects for the medicinal applications of P. vulgaris.