PMID: 

Int J Mol Sci. 2015 Jun 2 ;16(6):12424-35. Epub 2015 Jun 2. PMID: 26042464

Abstract Title: 

Induction of Apoptosis in Endometrial Cancer (Ishikawa) Cells by Pogostemon cablin Aqueous Extract (PCAE).

Abstract: 

Pogostemon cablin (PC) is a traditional herbal medicine used in the treatment of the common cold, nausea, diarrhea, and even for headaches and fever. However, the mechanisms underlying the anti-proliferative activity of PC in endometrial cancer (EC) cells have yet to be fully elucidated. This study investigated the anticancer effects of an aqueous extract of Pogostemon cablin (PCAE), specifically induced apoptosis in EC (Ishikawa) cells. Proliferation of EC cells following exposure to PCAE was assessed by an MTT assay. DNA content and the induction of cell cycle apoptosis were analyzed by flow cytometry (FACS Calibur). Protein caspase-3 and, -9 as well as AIF were investigated using Western blot. Our results demonstrate growth inhibition of Ishikawa cells by PCAE. Furthermore, caspase-3 activity caused PCAE-treated cell lines to accumulate in apoptosis. Gene expression profiling (GEP) results further suggest that, in addition to its known effects with regard to EC prevention, PCAE may also exert antitumor activity on established EC cells. Many previous studies have identified the chemo-preventive effects of natural plant materials and the potential role of these materials in chemotherapy. This current study used human EC Ishikawa cells to investigate the anti-tumor effects of PCAE in EC cells. Our results demonstrate that PCAE inhibits the growth of cancer cells and induces apoptosis, which suggests the potential applicability of PCAE as an antitumor agent.

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PMID: 

Int J Mol Med. 2016 Jan ;37(1):217-24. Epub 2015 Nov 3. PMID: 26531835

Abstract Title: 

Anti-allergic and anti-inflammatory effects of aqueous extract of Pogostemon cablin.

Abstract: 

Allergic disease is caused by exposure to normally innocuous substances that activate mast cells. Mast cell-mediated allergic inflammation is closely related to a number of allergic disorders, such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for treating allergic disease is an interesting subject and important to human health. The aim of the present study was to investigate the anti‑allergic and anti-inflammatory effects of the aqueous extract of Pogostemon cablin (Blanco) Benth (AEPC) (a member of the Labiatae family) using mast cells, and also to determine its possible mechanisms of action. An intraperitoneal injection of compound 48/80 or a serial injection of immunoglobulin E and antigen was used to induce anaphylaxis in mice. We found that AEPC inhibited compound 48/80‑induced systemic and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. The release of histamine from mast cells was reduced by AEPC, and this suppressive effect was associated with the regulation of calcium influx. In addition, AEPC attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated expression of pro-inflammatory cytokines in mast cells. The inhibitory effects of AEPC on pro-inflammatory cytokines were dependent on the activation of nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). AEPC blocked the PMACI-induced translocation of NF-κB into the nucleus by hindering the degradation of IκBα and the phosphorylation of p38 MAPK. Our results thus indicate that AEPC inhibits mast cell‑mediated allergic inflammation by suppressing mast cell degranulation and the expression of pro-inflammatory cytokines caused by reduced intracellular calcium levels and the activation of NF-κB and p38 MAPK.

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PMID: 

Exp Ther Med. 2016 Feb ;11(2):674-682. Epub 2015 Dec 8. PMID: 26893665

Abstract Title: 

Protective effects of patchouli alcohol isolated fromon lipopolysaccharide-induced acute lung injury in mice.

Abstract: 

Patchouli alcohol (PA) is a tricyclic sesquiterpene isolated from Pogostemon cablin, which exerts anti-inflammatory, anti-influenza and cognitive-enhancing bioactivities. The present study aimed to investigate the protective effects of PA on acute lung injury (ALI) induced by intratracheal instillation of lipopolysaccharide (LPS) in mice. Dexamethasone was used as a positive drug for protection against LPS-induced ALI. The results of the present study demonstrated that pretreatment with PA significantly increased survival rate, attenuated histopathologic damage and lung edema, and decreased the protein content in the bronchoalveolar lavage fluid (BALF) of mice with ALI. Furthermore, PA significantly inhibited the expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the BALF, downregulated the levels of myeloperoxidase and malondialdehyde, and upregulated the activity levels of superoxide dismutase and glutathione peroxidase in lung tissue. These results indicated that PA may exert potent protective effects against LPS-induced ALI in mice, the mechanisms of which are possibly associated with the anti-inflammatory and antioxidative activities of PA.

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PMID: 

Int Immunopharmacol. 2016 Jun ;35:43-52. Epub 2016 Mar 24. PMID: 27017292

Abstract Title: 

(-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.

Abstract: 

(-)-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 engagedin 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.

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PMID: 

Biomed Pharmacother. 2016 Oct ;83:930-935. Epub 2016 Aug 11. PMID: 27522255

Abstract Title: 

Patchouli alcohol attenuates experimental atherosclerosis via inhibiting macrophage infiltration and its inflammatory responses.

Abstract: 

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 asα-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.

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PMID: 

Biomed Res Int. 2016 ;2016:4567580. Epub 2016 Oct 17. PMID: 27830146

Abstract Title: 

Molecular Role of EGFR-MAPK Pathway in Patchouli Alcohol-Induced Apoptosis and Cell Cycle Arrest on A549 Cellsand.

Abstract: 

Nowadays, chemotherapy is still the main effective treatment for cancer. Herb prescriptions containing(also known as"Guang-Huo-Xiang") have been widely used in Chinese medicine today. In our research, we found that patchouli alcohol, a compound isolated from the oil of, exerted antitumor ability against human lung cancer A549 cells ability bothand. MTT assay was used to assess cell viability. Hoechst 33342 staining and TUNEL cover glass staining provided the visual evidence of apoptosis. Caspase activity measurement showed that patchouli alcohol activated caspase 9 and caspase 3 of mitochondria-mediated apoptosis. Consistently, patchouli alcohol inhibited the xenograft tumor. Further investigation of the underlying molecular mechanism showed that MAPK and EGFR pathway might contribute to the antitumor effect of patchouli alcohol. Our study proved that patchouli alcohol might be able to serve as a novel antitumor compound in the clinical treatment of lung cancer.

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PMID: 

Sci Rep. 2017 07 17 ;7(1):5591. Epub 2017 Jul 17. PMID: 28717228

Abstract Title: 

Transformation of patchouli alcohol toβ-patchoulene by gastric juice: β-patchoulene is more effective in preventing ethanol-induced gastric injury.

Abstract: 

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform intoβ-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.

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PMID: 

Mol Med Rep. 2017 Oct ;16(4):4511-4520. Epub 2017 Aug 2. PMID: 28791344

Abstract Title: 

T cell inhibition by pogostone from Pogostemon cablin (Blanco) Benth: In vitro and in vivo immunosuppressive analysis.

Abstract: 

Various plant-derived compounds exhibit immunosuppressive activity in pre‑clinical investigations, suggesting that they may serve as natural alternatives for the prevention of inflammatory disorders and autoimmune diseases. The aim of the current study was to explore the immunosuppressive potential of pogostone (PO) derived from Pogostemon cablin (Blanco) Benth. Carboxyfluorescein diacetate succinimidyl ester‑labeled cell tracking demonstrated that PO (20‑80 µM) inhibited Concanavalin A (ConA)‑stimulated lymphocyte proliferation, which was mediated by G0/G1 phase arrest and accompanied by significant decreases in the expression of CD69 (early‑stage activation marker) and CD25 (mid‑stage activation marker) in T cells, as indicated by flow cytometry analysis. Furthermore, the proliferation blocking ability of PO (5‑80 µM) was not associated with cytotoxicity in normal lymphocytes or apoptosis in ConA‑stimulated lymphocytes. The inflammatorycytokine profile determination using a cytometric beads assay revealed that PO inhibited release of anti‑inflammatory interleukin (IL)‑10 and pro‑inflammatory IL‑6 from the stimulated lymphocytes. Furthermore, PO (10, 20 or 40 mg/kg) ameliorated the T‑cell mediated delayed type hypersensitivity response in Balb/c mice by reducing leukocyte infiltration and tissue edema, providing a further validation of the direct immunosuppressive activity of PO. Together, the present data suggest that PO would suppress T cell response via a direct non‑cytotoxic inactivation at the early stage,accompanied by regulation of the inflammatory cytokine profile, which highlights clinical implications for treatment of immune-based disorders.

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PMID: 

Phytomedicine. 2018 Jan 15 ;39:111-118. Epub 2017 Dec 25. PMID: 29433672

Abstract Title: 

Protective role ofβ-patchoulene from Pogostemon cablin against indomethacin-induced gastric ulcer in rats: Involvement of anti-inflammation and angiogenesis.

Abstract: 

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used as effective anti-inflammatory agents. However, their clinical application brings about inevasible gastrointestinal side effects. Pogostemon cablin is a traditional herbal medicine used for the treatment of gastrointestinal diseases in China. One of its representative components, the tricyclic triterpenoidβ-patchoulone (β-PAE) has demonstrated great anti-inflammatory activity and gastroprotective effect against ethanol-induced gastric injury, but its protective effect against gastric ulcer induced by indomethacin is still unknown.PURPOSE: To assess the protective effect ofβ-PAE against ulcer produced by indomethacin and reveal the underlying pharmacological mechanism.STUDY DESIGN: We used an indomethacin-induced gastric ulcer model of rats in vivo.METHODS: Gastroprotective activity ofβ-PAE (10, 20, 40 mg/kg, i.g.) was estimated via indomethacin-induced gastric ulcer model in rats. Histopathological and histochemical assessment of ulcerated tissues were performed. Protein and mRNA expression were determined by Elisa, Western blotting and qRT-PCR.RESULTS: β-PAE could inhibit ulcer formation. Histopathological and histochemical assessment macroscopically demonstrated that β-PAE alleviates indomethacin-induced gastric ulceration in dose-dependent manner. After administration of β-PAE, elevated tumor necrosis factor -α level was significantly decreased and the phosphorylation of JNK and IκB was markedly inhibited. β-PAE suppressed the levels of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule and monocyte chemoattractant protein 1, as well as myeloperoxidase. Meanwhile, β-PAE increased cyclooxygenase enzyme activities (COX-1 and COX-2) to enhance the production of prostaglandin E. Proangiogenic protein, vascular endothelial growth factor and its receptor fms-like tyrosine kinase-1 mRNA expression were promoted while anti-angiogenic protein, endostatin-1 and its receptor ETAR mRNA expression were decreased.CONCLUSION: β-PAE may provide gastroprotection in indomethacin-induced gastric ulcer in rats by reducing inflammatory response and improving angiogenesis.

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PMID: 

Front Pharmacol. 2018 ;9:1347. Epub 2018 Nov 22. PMID: 30524287

Abstract Title: 

Unraveling the Novel Protective Effect of Patchouli Alcohol Against-Induced Gastritis: Insights Into the Molecular Mechanismand.

Abstract: 

Patchouli alcohol (PA), a natural tricyclic sesquiterpene extracted from(Blanco) Benth. (Labiatae), has been found to exhibit anti-and anti-inflammatory properties. In this study, we investigated the protective effect of PA againstinduced gastritisand, and determined the underlying mechanism. In theexperiment, a C57BL/6 mouse model of gastritis was established usingSS1, and treatments with standard triple therapy or 5, 10, and 20 mg/kg PA were performed for 2 weeks. Results indicated that PA effectively attenuated oxidative stress by decreasing contents of intracellular reactive oxygen species (ROS) and malonyldialdehyde (MDA), and increasing levels of non-protein sulfhydryl (NP-SH), catalase and glutathione (GSH)/glutathione disulphide (GSSG). Additionally, treatment with PA significantly attenuated the secretions of interleukin 1 beta (IL-1β), keratinocyte chemoattractant and interleukin 6 (IL-6). PA (20 mg/kg) significantly protected the gastric mucosa from-induced damage. In theexperiment, GES-1 cells were cocultured withNCTC11637 at MOI = 100:1 and treated with different doses of PA (5, 10, and 20μg/ml). Results indicated that PA not only significantly increased the cell viability and decreased cellular lactate dehydrogenase (LDH) leakage, but also markedly elevated the mitochondrial membrane potential and remarkably attenuated GES-1 cellular apoptosis, thereby protecting gastric epithelialcells against injuries caused by. PA also inhibited the secretions of pro-inflammatory factors, such as monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α) and IL-6. Furthermore, after PA treatment, the combination of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and cysteine-aspartic proteases 1 (CASPASE-1), the expression levels of NLRP3 inflammasome-related proteins, such as thioredoxin-interacting protein (TXNIP), pro-CASPASE-1, cle-CASPASE-1, and NLRP3 and genes (and) were significantly decreased as compared to the model group. In conclusion, treatment with PA for 2 weeks exhibited highly efficient protective effect against-induced gastritis and related damages. The underlying mechanism might involve antioxidant activity, inhibition of pro-inflammatory factor and regulation of NLRP3 inflammasome function. PA exerted anti-and anti-gastritis effects and thus had the potential to be a promising candidate for treatment of-related diseases.

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