patchouli-alcohol and Inflammation

Microglia-mediated neuroinflammation contributes to major depressive disorder (MDD). Targeting microglia is a promising strategy for treating MDD. Patchouli alcohol (PA), an active component of Pogostemon cablin, has anti-inflammatory and neuroprotective effects.. In this study, we investigate the microglia-mediated neurogenesis pathway in which PA ameliorates depressive-like behaviors in stress-induced animal model of depression.. C57BL/6J male mice were exposed to chronic mild stress (CMS) for 4 weeks, then administered PA intraperitoneally at 10, 20 or 40 mg/kg once per day for 3 weeks. The antidepressant effects of PA were evaluated in the sucrose preference test, forced swimming test, and tail suspension test. Microglial phenotypes and activation of the NLRP3 inflammation were analyzed using RT-PCR, western blotting and immunofluorescence staining. Effects of PA on neurogenesis were analyzed in vitro and in vivo using immunofluorescence staining.. Behavioral assessments showed that PA alleviated depressive-like behaviors in CMS-exposed mice. CMS induced microglial activation and pro-inflammatory profiles, which were blocked by PA treatment. PA attenuated the activation of NLRP3 inflammasome, leading to decreases in the levels of caspase-1, ASC, IL-1β, and IL-18 in the hippocampus of CMS-exposed mice. In primary microglia cultures, PA inhibited LPS-induced NLRP3 inflammasome activation. PA rescued inflammation-inhibited neurogenesis in vivo and in vitro.. Our results suggest that PA inhibits the NLRP3 inflammasome and ameliorates microglia-mediated neurogenesis impairment, contributing to antidepressant effects. Thus, PA may be a novel treatment for inflammation-driven mental disorders.

Topics: Animals; Antidepressive Agents; Depression; Depressive Disorder, Major; Inflammasomes; Inflammation; Male; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Stress, Psychological

Obesity impairs wound healing with substantial alterations in skin inflammation. Patchouli alcohol (PA), extracted from patchouli, has been reported to ameliorate inflammation in various cell types. However, the effects of PA on inflammation and wound healing have not been reported to date. In the present study, we examined whether PA affects cutaneous wound healing in high fat diet (HFD)-fed mice and explored PA-mediated molecular mechanisms through in vitro experiments. We found that PA administration accelerated wound healing as well as ameliorates inflammation in skin of HFD-fed mice. PA treatment augmented AMP-activated protein kinase (AMPK) phosphorylation and TGFb1 expression. PA enhanced cell migration and suppressed inflammation in LPS-treated HaCaT cells. Further, PA increased dose-dependently AMPK phosphorylation as along with TGFb1 and cell migration markers expression. siRNA for AMPK or TGFb1 abrogated the effects of PA on cell migration and inflammation. TGFb1 siRNA mitigated PA-induced expression of cell migration markers. These results suggest that PA ameliorates wound healing via AMPK and TGFb1-mediated suppression of inflammation. In sum, PA can be used as a novel treatment strategy for wound healing in obesity or insulin resistance.

Topics: AMP-Activated Protein Kinases; Animals; Cell Movement; Cell Proliferation; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; Sesquiterpenes; Transforming Growth Factor beta1; Wound Healing

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients' intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1β, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

Topics: Animals; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Fluorouracil; Gastrointestinal Microbiome; Inflammation; Intestinal Mucosa; Male; Mucositis; Myeloid Differentiation Factor 88; NF-kappa B; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Toll-Like Receptor 2

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, characterized by diarrhea, hematochezia, abdominal distension, and abdominal pain. The perpetuation of inflammation and the impairment of the intestinal barrier are part of the main courses of UC, responsible for the deteriorating inflammatory condition. Patchouli alcohol (PA), extracted from Pogostemon cablin Benth., is employed to treat both inflammation and intestinal barrier damage. Its curative effect on UC was testified firstly by TNBS-induced UC, a chemically induced colitis, and further tested by DSS-induced UC, an acute attack stage of UC in which the clinical course of human UC occurs frequently. PA reduced the levels of TNF-α, IFN-γ, IL-1β, IL-6, and IL-17 in serum and decreased the mRNA expression of pro-inflammatory cytokines (e.g., iNOS, COX-2, TNF-α, IL-1β, and IL-6). Concurrently, PA upregulated the expression of tight junction protein (e.g., ZO-1, ZO-2, claudin-1, and occludin) and the mRNA of mucin-1 and mucin-2 in both animal models. Further, PA ameliorated both histological damage and clinical parameters. Thus, PA could credibly reduce the expression of pro-inflammatory cytokines, protect the integrity of intestinal epithelial barrier, and repair the macroscopic colon lesions in both colitis models.

Topics: Animals; Colitis, Ulcerative; Dextran Sulfate; Female; Inflammation; Intestinal Mucosa; Male; Mice; Mice, Inbred BALB C; Rats; Rats, Sprague-Dawley; Sesquiterpenes

(-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions.

Topics: Apoptosis; Bacterial Proteins; Catalysis; Cell Line; Cytokines; Cytoprotection; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Intestinal Mucosa; Oxidative Stress; Pogostemon; Sesquiterpenes; Urease

Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from a traditional Chinese herb pogostemonis herba. Literatures have proven that PA could inhibit inflammatory responses in various inflammatory disease models. However, whether PA could protect against atherosclerosis, a chronic vascular inflammation, is unknown. In this study, we sought to explore this issue in atherosclerosis-prone apolipoprotein E knockout mice fed an atherogenic diet, with or without daily PA intragastrical administration (40mg/kg). Our results showed that PA administration did not change plasma lipids metabolism, however, it significantly attenuated atherosclerotic plaque burdens in both the aorta and the aortic root. The lesional macrophage content, shown as Mac2 positive areas, was reduced, while the lesional smooth muscle cell and collagen content, shown as α-SMA positive areas and by Sirius red staining, respectively, was not affected in PA-treated mice, compared with non-treated controls. Aortic mRNA expression of macrophage inflammatory cytokines, including MCP-1, iNOS, IL-1β, IL-6, CXCL9 and CXCL11, was also reduced in PA-treated mice. Therefore, we demonstrated that PA could attenuate atherosclerosis, possibly by inhibiting macrophage infiltration and its inflammatory responses.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Gene Expression Regulation; Inflammation; Lipid Metabolism; Lipids; Macrophages; Mice; Mice, Knockout; Plaque, Atherosclerotic; Sesquiterpenes

The aim of this study was to evaluate the effect of Pogostemon cablin essential oil (PEO) on leukocyte behavior in the inflammatory response.. PEO was analyzed using Gas Chromatography/Mass Spectrometry (GC/SM) and Nuclear Magnetic Resonance Spectroscopy (NMR) methods and showed predominance of patchoulol (38.50%), α-bulnesene (20.37%), α-guaiene (12.31%), seychellene (8.33%) and α-patchoulene (4.91%). PEO at concentrations of 1, 3, 10, 30, 60 and 90μg/ml reduced the in vitro neutrophil chemotaxis toward fMLP, and at concentrations of 3 and 10μg/ml, increased the phagocytic activity of neutrophils. Topical application of PEO in high concentrations promoted an increase of ear edema and myeloperoxidase (MPO) activity. However, the oral treatment with 100, 200 and 300mg/kg reduced leukocyte recruitment, nitric oxide (NO) production, and rolling and adherent leukocyte number in the microcirculation.. PEO affects the leukocyte behavior, and the mechanism proposed of PEO seems to be, at least in part, involving the participation of NO and pro-inflammatory cytokines.

Topics: Acute Disease; Administration, Topical; Animals; Cell Adhesion; Cell Survival; Chemotaxis; Edema; Exudates and Transudates; Gas Chromatography-Mass Spectrometry; Inflammation; Leukocyte Count; Leukocyte Rolling; Leukocytes; Male; Mice; Nitric Oxide; Peritonitis; Peroxidase; Phagocytosis; Pogostemon; Sesquiterpenes; Zymosan

Pogostemonis Herba has long been used in traditional Chinese medicine for the treatment of inflammatory disorders. Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, is known to possess a variety of pharmacological activities. The present study aimed to investigate the in vivo anti-inflammatory effect of PA using two common inflammatory animal models i.e., xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. The degree of edema in both inflammatory animals, as well as the protein and mRNA expression of some inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E₂ (PGE₂) and nitric oxide (NO) in the hind paw of carrageenan-treated rats were measured. Results showed that PA (10-40 mg/kg) significantly inhibited the ear edema induced by xylene in mice and the paw edema induced by carrageenan in rats. In addition, treatment with PA (10-40 mg/kg) also dose-dependently decreased the production of TNF-α, IL-1β, PGE₂ and NO in the hind paw of carrageenan-treated rats. Furthermore, PA treatment also suppressed the mRNA expression of TNF-α, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hind paw of carrageenan-treated rats. These results suggest that PA possesses potent anti-inflammatory activity, which may be mediated, at least in part, by down-regulating the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-1β, iNOS and COX-2.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drugs, Chinese Herbal; Edema; Female; Inflammation; Inflammation Mediators; Lamiaceae; Male; Mice; Mice, Inbred Strains; Phytotherapy; RNA, Messenger; Sesquiterpenes; Xylenes