Phytochemicals: Current strategy to sensitize cancer cells to cisplatin.

Cisplatin-based chemotherapeutic regimens are the most frequently used adjuvant treatments for many types of cancer. However, the development of chemoresistance to cisplatin results in treatment failure. Despite the significant developments in understanding the mechanisms of cisplatin resistance, effective strategies to enhance the chemosensitivity of cisplatin are lacking. Phytochemicals are naturally occurring plant-based compounds that can augment the anti-cancer activity of cisplatin, with minimal side effects. Notably, some novel phytochemicals, such as curcumin, not only increase the efficacy of cisplatin but also decrease toxicity induced by cisplatin. However, the exact mechanisms underlying this process remain unclear. In this review, we discussed the progress made in utilizing phytochemicals to enhance the anti-cancer efficacy of cisplatin. We also presented some ideal phytochemicals as novel agents for counteracting cisplatin-induced organ damage.

Different effects of (+)­borneol and (­)­borneol on the pharmacokinetics of osthole in rats following oral administration.

Osthole is the primary active component of a number of herbal plants such as the Cnidium monnieri fruit. In traditional Chinese herb medicine, osthole is commonly used in combination with borneol to obtain improved pharmacological effects. The aim of the present study was to investigate the effect of borneol enantiomers on the pharmacokinetics of osthole. An appropriate high­performance liquid chromatography (HPLC) method was applied to determine the concentrations of osthole in plasma. Following oral administration of osthole alone or combined with borneol in rats, blood samples were collected and analyzed by HPLC. The results demonstrated that there were statistically significant differences in the pharmacokinetic parameters of osthole between osthole administration alone and co­administration with borneol. When combined with synthetic borneol, the AUC0­t, AUC0­∞ and Cmax of osthole increased by 48.153, 104.708 and 92.630%, respectively, while the CL/F decreased by 51.251%. When combined with (+)­borneol, the AUC0­t, AUC0­∞ and Cmax of osthole were increased by 61.561, 78.167, and 51.769%, respectively, while the CL/F decreased by 44.174% (P<0.01). In addition, when combined with (­)­borneol, the AUC0­t, AUC0­∞ and Cmax of osthole increased by 115.856, 167.786 and 271.289%, respectively, while the CL/F decreased by 60.686% (P<0.01). These results indicated that borneol may enhance gastrointestinal absorption and inhibit the metabolism of osthole. In addition, the promotional effect of (­)­borneol on the pharmacokinetic parameters of osthole was greater than that of (+)­borneol.

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-ß1 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.

Kegan Liyan oral liquid ameliorates lipopolysaccharide-induced acute lung injury through inhibition of TLR4-mediated NF-κB signaling pathway and MMP-9 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Kegan Liyan oral liquid (KGLY), a Chinese prescription modified from classic formulas Yin-Qiao-San (from TCM classic Wenbing Tiaobian) and Shen-Jie-San (first mentioned in Shanghan Wenyi Tiaobian), has been reported to exert heat-clearing and detoxifying effects and used extensively for the treatment of severe pulmonary diseases in clinics including influenza, cough and pneumonia. AIM OF THIS STUDY: The purpose of this study was to investigate the protective effect of KGLY on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with KGLY (50, 100 and 150mg/kg) before intratracheal instillation of LPS. 24h post LPS challenge, lung tissues and the bronchoalveolar lavage fluid (BALF) were collected for lung wet/dry (W/D) weight ratio, histopathological examinations and biochemical analyses. The cell counts, protein concentration, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) in BALF, superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO) and malondialdehyde (MDA) levels were detected. Meanwhile, the activation of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), as well as matrix metalloproteinases 9 (MMP-9) were determined by western blot assay. RESULTS: KGLY significantly prolonged mice survival time and ameliorated LPS-induced edema, thickening of alveolar septa and inflammatory cell infiltration in a dose-dependent manner. Additionally, KGLY markedly attenuated LPS-induced acute pulmonary inflammation via decreasing the expressions of cytokines and chemokines (IL-1ß, IL-6, TNF-α, and MIP-2), enhanced the activities of anti-oxidative indicators (SOD and GSH), suppressed the levels of MPO and MDA, and down-regulated the expressions of TLR4, NF-κB and MMP9. CONCLUSIONS: The results suggested that the relieving effect of KGLY against LPS-induced ALI might be partially due to suppression of oxidative stress and inflammatory response, inhibition of TLR4-mediated NF-κB activation, and down-regulation of MMP9 expression, indicating it may be a potential therapeutic agent for ALI.

Protective effects of pogostone against LPS-induced acute lung injury in mice via regulation of Keap1-Nrf2/NF-κB signaling pathways.

Pogostone, a major component of Pogostemon cablin, has been demonstrated to possess antibacterial, anti-fungal, immunosuppressive and anti-inflammatory properties. To investigate the potential therapeutic effect of pogostone on lipopolysaccharide (LPS)-induced acute lung injury (ALI), mice were pretreated with pogostone prior to LPS exposure. After LPS challenge, the lungs were excised and the histological changes, wet to dry weight ratios, MPO activity reflecting neutrophil infiltration, and MDA activity reflecting oxidative stress were examined. The inflammatory cytokines in the BALF were determined by ELISA assay. Moreover, the expressions of p65 and phosphorylated p65 subunit of NF-κB, and Nrf2 in the nucleus in lung tissues were measured by Western blot analysis, and meanwhile the dependent genes of NF-κB and Nrf2 were assessed by RT-qPCR. The results showed that pretreatment with pogostone markedly improved survival rate, attenuated the histological alterations in the lung, reduced the MPO and MDA levels, decreased the wet/dry weight ratio of lungs, down-regulated the level of pro-inflammatory mediators including TNF-a, IL-1ß and IL-6. Furthermore, pretreatment with pogostone enhanced the Nrf2 dependent genes including NQO-1, GCLC and HO-1 but suppressed NF-κB regulated genes including TNF-α, IL-1ß and IL-6. The mechanism behind the protective effect was correlated with its regulation on the balance between Keap1-Nrf2 and NF-κB signaling pathways. Therefore, pogostone may be considered as a potential therapeutic agent for preventing and treating ALI.