Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS: TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

Electroacupuncture for relieving itching in atopic eczema: study protocol for a multicenter, randomized, sham-controlled trial.

Background: Atopic eczema (AE) is a common atopic inflammatory skin disease affecting 2.1-4.9% of the population in different countries. Pruritus, one of the most burdensome symptoms, is often underestimated for the problems it can cause, creating a vicious loop of itching, scratching, and lichenification. Therefore, further research into practical and safe treatments that relieve itchy symptoms and enhance skin protection is key to overcoming AE. Acupuncture, with or without electrical stimulation, is one of the most commonly used therapeutic measures to treat AE. This trial aimed to objectively evaluate the efficacy and safety of the electroacupuncture (EA) antipruritic technique in AE pruritus and obtain high-level clinical evidence for the popularization and application of EA for AE. Methods and analysis: This multicenter, single-blinded, randomized controlled trial is planned to transpire from April 15, 2023, to June 30, 2025. We will recruit 132 participants with AE (44 per group). Participants will be assigned randomly to three equal-sized groups: EA, sham electroacupuncture, and sham acupuncture. Treatment will be administered three times a week during the 2-week intervention phase. The primary outcome measure is the Visual Analog Scale, with a numeric rating scale to evaluate pruritus. Secondary outcome measures include the Eczema Area and Severity Index and Dermatology Life Quality Index. Other outcome measures include physical examination, serum IgE, and safety evaluation. The number, nature, and severity of adverse events will be carefully recorded. Trial registration: ClinicalTrials.gov, 22Y11922200. Registered 3 September 2022, https://register.clinicaltrials.gov.

Evidence and Potential Mechanism of Action of Lithospermum erythrorhizon and Its Active Components for Psoriasis.

Background: Traditional Chinese medicine is effective in the treatment of psoriasis and can significantly reduce skin inflammation and psoriatic lesions with minimal side effects. Shikonin (SHI) and ß,ß-dimethylacryloyl alkannin (DMA), the main active components of Lithospermum erythrorhizon, have strong anti-inflammatory effects. This systematic review aimed to evaluate the efficacy and safety of Lithospermum erythrorhizon and its main active components and to elucidate the potential mechanisms of their action in psoriasis treatment. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Scientific Journals, Wan Fang, and Chinese Biomedicine databases were systematically searched for articles published between 1 January 1970, and 31 February 2021. We included clinical and preclinical studies that examined the effects of Lithospermum erythrorhizon and its active components on psoriasis. All data were analyzed using RevMan 5.3 software. The Cochrane and SYRCLE's risk-of-bias tools were used to assess the quality of all studies. Results: Eleven clinical trials including 1024 participants and 23 preclinical studies were assessed. Meta-analysis showed that when treating patients with psoriasis, the Chinese herbal medicine (CHM) formulas with Lithospermum erythrorhizon as the sovereign herb can significantly improve psoriatic dermatitis, which can significantly reduce the psoriasis area and severity index (PASI) score (mean difference [MD] = -2.00, 95% confidence interval [CI] [-3.19, -0.80], p = 0.001; I2 = 85%). The incidence rates of diarrhea (risk ratio = 0.21, 95% CI [0.06, 0.81], p = 0.02) were higher in the CHM formulas group than in the control group, whereas other adverse events were not significantly different between the two groups (p > 0.05). We evaluated the PASI score of mice on day 7 and found that SHI and DMA also alleviated psoriatic lesions (MD = -3.36, 95% CI [-4.67, -2.05], p < 0.00001, I2 = 94%). Furthermore, the epidermal thickness decreased more after SHI or DMA treatment than in the control group (MD = -34.42, 95%CI [-41.25, -27.59], p < 0.00001, I2 = 93%). Based on preclinical studies, we also summarized and mapped the mechanisms of SHI and DMA in the treatment of psoriasis. Conclusion: Available findings demonstrated that Lithospermum erythrorhizon combined with other conventional treatments is useful in treating psoriasis. Preclinical evidence has shown that the active components of Lithospermum erythrorhizon exhibit a potential anti-inflammatory effect, promote keratinocyte apoptosis, inhibit keratinocyte proliferation and angiogenesis, and block the cell cycle. In summary, our findings suggest that Lithospermum erythrorhizon and its active components can be used to treat psoriasis.

Fire Needle Therapy for the Treatment of Psoriasis: A Quantitative Evidence Synthesis.

Background: Fire needle therapy is a method of quickly piercing into acupoints with red-hot needles to treat diseases. Recently, multiple studies have reported that fire needle therapy is effective in the treatment of psoriasis; however, there are few articles systematically evaluating the effect of this therapy. Therefore, this systematic and meta-analysis study is conducted to estimate the efficacy and safety of fire needle therapy for psoriasis. Methods: PubMed, Embase, CNKI, VIP, CBM, CENTRAL, and Wan Fang databases were systematically searched from the dates of construction of these databases to August 24, 2019, and randomized controlled trials assessing patients with psoriasis who were treated with fire needle therapy alone or in combination with other drugs were also evaluated. Results: Fire needle therapy was effective in treating psoriasis (p = 0.0002; risk ratio [RR], 1.20; 95% confidence interval [CI], 1.09-1.33) with a lower recurrence rate (p = 0.005; RR, 0.48; 95% CI, 0.29-0.80). Adverse events after fire needle treatment were similar to those without fire needle treatment (p = 0.38; RR, 0.67; 95% CI, 0.28-1.63). After fire needle treatment, the number of cluster of differentiation (CD)8+T cells, type 1 helper cells, interleukin (IL)-2, and interferon (IFN)-γ decreased, whereas the number of CD4+T cells, type 2 helper cells, IL-4, IL-10, and the proportion of CD4+T cells and CD8+T cells increased. Conclusions: Fire needle therapy, specifically in combination with oral medicines, is effective in treating patients with psoriasis with low recurrence rates.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.

Uncovering the mechanism of Jueyin granules in the treatment of psoriasis using network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Our clinical practice demonstrated that Jueyin granules (JYG) benefit patients with mild to moderate psoriasis vulgaris without apparent adverse effects. JYG have been shown to inhibit epidermal proliferation in an imiquimod (IMQ)-induced psoriasis-like mouse model, as well as keratinocyte proliferation. Moreover, JYG causes no acute or chronic toxicity in animal models. However, its related molecular mechanism has still not been elucidated. AIM OF THE STUDY: To assess the mechanism of JYG against psoriasis. MATERIALS AND METHODS: This study combined network pharmacology analysis with experiments to investigate the mechanism of JYG against psoriasis. First, the molecular docking technology was used to construct the network of medicinal materials-core active plant ingredients-core targets and identify possible drug targets. Next, high-performance liquid chromatography (HPLC) was used for quality control of JYG. Finally, a mice model of psoriasis was used to further verify the effects of JYG. RESULTS: (1) Molecular docking analysis of network pharmacology revealed that the therapeutic effects of JYG on psoriasis might be achieved through Vitamin D Receptor (VDR) effects. (2) The concentrations of chlorogenic acid and paeoniflorin were determined using HPLC to establish quality control of JYG. (3) JYG ameliorated pathological characteristics that included in vivo reductions in erythema, scale, and infiltration scores of back and ear lesions in IMQ-induced psoriasis-like mice. Moreover, a reduced number of PCNA-positive and Ki67-positive cells were observed in the epidermis of JYG-treated lesions. JYG also reduced inflammation (interleukin (IL)-17, IL-23) in the peripheral blood of IMQ-induced psoriasis-like mice. As expected, JYG was found to upregulate VDR expression and downregulate p-STAT3 expression in the IMQ group, which may contribute to its mechanism against psoriasis. CONCLUSION: Overall, this study clarifies the mechanism of JYG against psoriasis and provides evidence to support its clinical use.

Identification of Transient Receptor Potential Vanilloid 3 Antagonists from Achillea alpina L. and Separation by Liquid-Liquid-Refining Extraction and High-Speed Counter-Current Chromatography.

Bioassay-guided fractionation of the ethanol extract of whole herbs of Achillea alpina led to the isolation of isochlorogenic acids A and B as transient receptor potential vanilloid 3 (TRPV3) channel antagonists by using a calcium fluorescent assay. The structures were identified by spectroscopic analysis and the inhibitory activities of isochlorogenic acids A and B were confirmed by whole-cell patch clamp recordings of human embryonic kidney 293 (HEK293) cells expressing human TRPV3. Molecular docking results revealed that these two compounds reside in the same active pocket of human TRPV3 channel protein with lower binding energy than the agonist 2-aminoethoxydiphenyl borate (2-APB). High-speed counter-current chromatography (HSCCC) coupled with a liquid-liquid extraction approach was successfully established for the separation of isochlorogenic acids A and B from the whole herbs of A. alpina. Ethyl acetate and n-hexane-ethyl acetate-water (3:3:4 and 1:5:4, v/v/v) were selected as liquid-liquid extraction solvent systems to remove high- and low-polarity impurities in the mixture. Sixty g of ethanol extract was refined by solvent partition to yield 1.7 g of the enriched fraction, of which 480 mg in turn obtained 52.5 mg of isochlorogenic acid B (purity 98.3%) and 37.6 mg isochlorogenic acid A (purity 96.2%) after HSCCC with n-hexane-ethyl acetate-water containing 1% acetic acid (1:4:8, v/v/v).

Antipruritic Effect of Natural Coumarin Osthole through Selective Inhibition of Thermosensitive TRPV3 Channel in the Skin.

Coumarin osthole is a dominant bioactive ingredient of the natural Cnidium monnieri plant commonly used for traditional Chinese herbal medicines for therapies and treatments including antipruritus and antidermatitis. However, the molecular mechanism underlying the action of osthole remains unclear. In this study, we report that osthole exerts an antipruritic effect through selective inhibition of Ca2+-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) cation channels that are primarily expressed in the keratinocytes of the skin. Coumarin osthole was identified as an inhibitor of TRPV3 channels transiently expressed in HEK293 cells in a calcium fluorescent assay. Inhibition of the TRPV3 current by osthole and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV3-expressing HEK293 cells and mouse primary cultured keratinocytes. Behavioral evaluation demonstrated that inhibition of TRPV3 by osthole or silencing by knockout of the TRPV3 gene significantly reduced the scratching induced by either acetone-ether-water or histamine in localized rostral neck skin in mice. Taken together, our findings provide a molecular basis for use of natural coumarin osthole from the C. monnieri plant in antipruritic or skin care therapy, thus establishing a significant role of the TRPV3 channel in chronic itch signaling or acute histamine-dependent itch sensation.

Selective Activation of Nociceptor TRPV1 Channel and Reversal of Inflammatory Pain in Mice by a Novel Coumarin Derivative Muralatin L from Murraya alata.

Coumarin and its derivatives are fragrant natural compounds isolated from the genus Murraya that are flowering plants widely distributed in East Asia, Australia, and the Pacific Islands. Murraya plants have been widely used as medicinal herbs for relief of pain, such as headache, rheumatic pain, toothache, and snake bites. However, little is known about their analgesic components and the molecular mechanism underlying pain relief. Here, we report the bioassay-guided fractionation and identification of a novel coumarin derivative, named muralatin L, that can specifically activate the nociceptor transient receptor potential vanilloid 1 (TRPV1) channel and reverse the inflammatory pain in mice through channel desensitization. Muralatin L was identified from the active extract of Murraya alata against TRPV1 transiently expressed in HEK-293T cells in fluorescent calcium FlexStation assay. Activation of TRPV1 current by muralatin L and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV1-expressing HEK-293T cells and dorsal root ganglion neurons isolated from mice. Furthermore, muralatin L could reverse inflammatory pain induced by formalin and acetic acid in mice but not in TRPV1 knock-out mice. Taken together, our findings show that muralatin L specifically activates TRPV1 and reverses inflammatory pain, thus highlighting the potential of coumarin derivatives from Murraya plants for pharmaceutical and medicinal applications such as pain therapy.

[Controlled observation on catgut implantation at acupoint for treatment of prolapse of lumbar intervertebral disc].

OBJECTIVE: To compare therapeutic effects of catgut implantation at acupoint and routine acupuncture on prolapse of lumbar intervertebral disc. METHODS: One hundred and forty cases were randomly divided into a treatment group and a control group, 70 cases in each group. The treatment group were treated with catgut implantation at acupoint, once each week, 3 sessions constituting one course, and the control group with routine acupuncture, once every other day, 10 sessions constituting one course. RESULTS: The effective rate was 95.6% after treatment of one course and 88.2% 3 months later in the treatment group, which were better than 84.6% and 72.3% in the control group, respectively (Both P < 0.05). CONCLUSION: Catgut implantation at acupoint has a better therapeutic effect on prolapse of lumbar intervertebral disc, with lower cost.