Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p‐AKT, Bcl‐2, cyclin D1, and CDK4 but increased the expression of Bax, GSK‐3β, clv‐caspase‐3, and clv‐caspase‐9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.

Context: Shaoyao Gancao Decoction (SGD), a famous herbal medicine, consists of two herbs (Paeoniae Radix and Glycyrrhizae Radix) and is traditionally used for the treatment of pain. Objective: To investigate the synergistic potential of total glucosides of Paeoniae Radix (TGP) and total flavonoids of Glycyrrhizae Radix (TFL). Materials and methods: Oral administration of TGP and TFL alone at the doses of 60,120 and 240 mg/kg or in combination were given only one time to the neuropathic pain rat induced by chronic constriction injury. Paw pressure and heat immersion tests were performed to assess degrees of mechanical allodynia and thermal hyperalgesia, respectively. Synergistic interactions between TGP and TFL were characterized using isobolographic analysis. Expressions of Sirt1 protein were detected by immunohistochemistry. Results and discussion: On day 14 after surgery, single oral administration of TGP and TFL both produced significant anti-allodynic and anti-hyperalgesic effects in dose-dependent and time-dependent manners. The ED₅₀ value of TGP was 249.4 ± 10.8 mg/kg while TFL was 871.4 ± 30.5 mg/kg. Isobolographic analysis revealed that the combination of TGP with TFL at the fixed ratios of 3:1 exerted the highest sub-additive (synergistic) interaction, of which the experimental ED₅₀ value was 95.1 ± 9.0 mg/kg. SGD could also downregulate Sirt1 protein expression, which was 4.2-fold higher than that of model rats in dorsal root ganglion. Conclusion: Analgesic effects of SGD may contribute to simultaneous inhibition of Sirt1 overexpression and could warrant further evaluation as a possible agent for the treatment of neuropathic pain.