Jia-Li Liang

Anti-inflammatory activity of β-patchoulene isolated from patchouli oil in mice.

β-Patchoulene (β-PAE) is a tricyclic sesquiterpene isolated from the oil of Pogostemon cablin (patchouli oil), which has been widely used in traditional Chinese medicine for the treatment of inflammatory diseases. However, as one of the major principle of patchouli oil, the biological activity of β-PAE has not been explored so far. In the present study, the anti-inflammatory activity in vivo, and the underlying mechanism, of β-PAE was investigated on experimental mice models of acute inflammation, i.e. xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results showed that β-PAE evoked a significant dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan and suppressed the increase of vascular permeability elicited by acetic acid. Histopathological analysis indicated that β-PAE could markedly decrease the cellular infiltration in paw tissue. β-PAE was also shown to significantly decrease the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in edema paw. In addition, carrageenan-induced production of some pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO), were suppressed in a dose-dependent manner in mice subjected to β-PAE pretreatment, and it also significantly down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further analysis revealed that β-PAE also inhibited the translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus and stabilize the conversion of nuclear factor-κBα (IκBα) level. These results provided additional chemical and pharmacological basis for the traditional application of P. cablin in inflammatory disorders.

Anti-Fatigue and Antioxidant Activity of the Polysaccharides Isolated from Millettiae speciosae Champ. Leguminosae

Millettiae speciosae Champ. Leguminosae (MSC), is a well-known Chinese herb traditionally used as food material and medicine for enhancing physical strength. Our preliminary study found that the aqueous extract of this herb (MSE) had an anti-fatigue effect. In this paper, we further separated MSE into total polysaccharides (MSP) and supernatant (MSS) by alcohol precipitation, and explored which fraction was active for its anti-fatigue effect. Mice were orally administered with MSP or MSS at the doses of 200, 400, and 800 mg/kg for 20 days and the anti-fatigue effect was assessed by exhaustive swimming exercise (ESE). The biochemical parameters related to fatigue after ESE and the in vitro antioxidant activity of active fraction were determined. Our results showed that MSP, instead of MSS, significantly extended the swimming time to exhaustion (p < 0.05), indicating that MSP is responsible for the anti-fatigue effect of MSE. In addition, MSP treatment increased the levels of glucose (Glu) and muscle glycogen, whereas it decreased the accumulations of blood urea nitrogen (BUN) and lactic acid (Lac). Moreover, ESE increased the levels of creatine phosphokinase (CK), lactic dehydrogenase (LDH), and malondialdehyde (MDA) but reduced superoxide dismutase (SOD) and glutathione (GSH) in plasma. In contrast, MSP inhibited all the above changes relating to fatigue. Furthermore, an in vitro antioxidant test revealed that MSP dose-dependently scavenged ·OH and DPPH free radicals. Taken together, these findings strongly suggested that MSP was able to alleviate physical fatigue by increasing energy resources and decreasing accumulation of detrimental metabolites. The antioxidant activity may crucially contribute to the observed anti-fatigue effect of MSP.

Anti-inflammatory activity of coptisine free base in mice through inhibition of NF-κB and MAPK signaling pathways

Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan. Additionally, CFB significantly suppressed the productions of interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKβ, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.

Patchoulene Epoxide Isolated from Patchouli Oil Suppresses Acute Inflammation through Inhibition of NF-κB and Downregulation of COX-2/iNOS

According to the GC-MS analysis, compositional variation was observed between samples of patchouli oil, of which an unknown compound identified as patchoulene epoxide (PAO) was found only in the long-stored oil, whose biological activity still remains unknown. Therefore, the present study aimed to evaluate the potential anti-inflammatory activity with three in vivo inflammatory models: xylene-induced ear edema, acetic acid-induced vascular permeability, and carrageenan-induced paw edema. Further investigation into its underlying mechanism on carrageenan-induced paw edema was conducted. Results demonstrated that PAO significantly inhibited the ear edema induced by xylene, lowered vascular permeability induced by acetic acid and decreased the paw edema induced by carrageenan. Moreover, PAO markedly decreased levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO), but increased levels of interleukin-4 (IL-4) and interleukin-10 (IL-10). PAO was also shown to significantly downregulate the protein and mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitric-oxide synthase (iNOS). Western blot analysis revealed that PAO remarkably inhibited p50 and p65 translocation from the cytosol to the nucleus by suppressing IKKβ and IκBα phosphorylation. In conclusion, PAO exhibited potent anti-inflammatory activity probably by suppressing the activation of iNOS, COX-2 and NF-κB signaling pathways.

Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

Bleomycin (BLM), a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22) tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6), tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

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

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 into β-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.

Patchouli oil isolated from the leaves of Pogostemon cablin ameliorates ethanol-induced acute liver injury in rats via inhibition of oxidative stress and lipid accumulation

Correction for ‘Patchouli oil isolated from the leaves of Pogostemon cablin ameliorates ethanol-induced acute liver injury in rats via inhibition of oxidative stress and lipid accumulation’ by Qiong-Hui Huang et al., RSC Adv., 2018, 8, 24399–24410.

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

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 triterpenoid β-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 of β-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 of β-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 E2. 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.

Polydatin protects against acetaminophen-induced hepatotoxicity in mice via anti-oxidative and anti-apoptotic activities

Acetaminophen (APAP) is commonly used to relieve pain and fever in a clinical setting, but its excessive use can lead to serious hepatotoxicity. Our previous study demonstrated that polydatin (PD) can effectively attenuate d-galactose- and alcohol-induced hepatotoxicity, however, its effect on APAP-induced hepatotoxicity is still unknown. In this study, we explore the protective effect and potential mechanism of PD against APAP-induced hepatotoxicity in mice. The results indicate that PD effectively improves the survival of mice with APAP-induced hepatotoxicity, significantly alleviating histopathologic alterations in the liver, and decreasing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). PD significantly and dose-dependently reduces oxidative stress by lowering the content of oxidized glutathione (GSSG), reactive oxygen species (ROS), nitric oxide (NO) and malonaldehyde (MDA), while enhancing the hepatic activities of glutathione (GSH), glutathione peroxidase (GSH-Px) and the GSH/GSSG ratio. Meanwhile, PD also substantially inhibits the levels and mRNA expressions of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (NOX2). Additionally, PD markedly arrests apoptosis by assuaging TUNEL-positive hepatocytes and the apoptotic index, decreasing the levels and expression of cytochrome c (CytC), cleaved-caspase-9, apoptotic protease activating factor 1 (Apaf-1), cleaved-caspase-3, and Bax and increasing the level and expression of Bcl-2. Overall, PD pretreatment shows a potent protective effect against APAP-induced hepatotoxicity by relieving oxidative stress and inhibiting apoptosis.

Comparison of anti-inflammatory effect between β-patchoulene epoxide and β-patchoulene in LPS-stimulated RAW264.7 macrophages

β-patchoulene (β-PAE) is one of the essential tricyclic sesquiterpenes of patchouli oil while β-patchoulene epoxide (β-PAO) is the oxidative product of β-PAE which can only be found in the oil with long storage period. Our previous researches demonstrated that both β-PAE and β-PAO exert potent anti-inflammatory activity in vivo, but which one is more valuable still remains uncertain. Therefore, this study adopts the model of LPS-stimulated RAW264.7 macrophages to compare β-PAO with β-PAE on the anti-inflammatory activity. According to our results, β-PAO was superior to β-PAE on anti-inflammation as evidence by lowering the protein and mRNA expressions of several pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-1β (IL-1β), and monocyte chemotactic protein-1 (MCP-1). β-PAO was also better than β-PAE in reducing the productions of nitric oxide (NO) and prostaglandin E2 (PGE2) through inhibiting inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 signaling pathway. The results above provided experimental basis for the conclusion that β-PAO was more potent than β-PAE in anti-inflammatory activity in vitro.