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The root of Croton crassifolius has been used as a traditional Chinese medicine (TCM), called Radix Croton Crassifolius, and commonly known as "Ji Gu Xiang" in Chinese. Its medicinal value has been recorded in several medical books or handbooks, such as "Sheng Cao Yao Xing Bei Yao", "Ben Cao Qiu Yuan" and "Zhong Hua Ben Cao". It has been traditional employed for treating sore throat, stomach-ache, rheumatism and cancer. At present, there are limited studies on the evaluation of low-polarity extracts of roots in C. crassifolius. Consequently, the aim of this study was to evaluate the antitumor effect of the low-polarity extract of C. crassifolius root. Extracts were obtained by supercritical fluid extraction. The extracts were tested for antitumor effects in vitro on several cancer cell lines. A CCK-8 kit was used for further analysis of cell viability. A flow cytometer and propidium iodide staining were used to evaluate the cell cycle and apoptosis. Hoechst staining, JC-1 staining and the fluorescence probe DCFH-DA were used to evaluate apoptotic cells. Molecular mechanisms of action were analyzed by quantitative RT‒PCR and Western blotting. Immunohistochemistry was used for the evaluation of xenograft tumors in male BALB/c mice. Finally, molecular docking was employed to predict the bond between the desired bioactive compound and molecular targets. Eleven diterpenoids were isolated from low-polarity C. crassifolius root extracts. Among the compounds, chettaphanin II showed the strongest activity (IC 50 = 8.58 μM) against A549 cells. Evaluation of cell viability and the cell cycle showed that Chettaphanin II reduced A549 cell proliferation and induced G2/M-phase arrest. Chttaphanin II significantly induced apoptosis in A549 cells, which was related to the level of apoptosis-related proteins. The growth of tumor tissue was significantly inhibited by chettaphanin II in experiments performed on naked mice. The antitumor mechanism of chettaphanin II is that it can obstruct the mTOR/PI3K/Akt signaling pathway in A549 cells. Molecular docking established that chettaphanin II could bind to the active sites of Bcl-2 and Bax. Taken together, the natural diterpenoid chettaphanin II was identified as the major antitumor active component, and its potential for developing anticancer therapies was demonstrated for the first time by antiproliferation evaluation in vitro and in vivo. [Display omitted] • Eleven diterpenoids were obtained from the SFE extract of C. crassifolius roots. • Chettaphanin II showed the strongest antitumor activity against A549 cells. • Chettaphanin II inhibited A549 cell proliferation and arrested cells in G2/M-phase. • Chettaphanin II induced A549 cell apoptosis by inhibiting PI3K/AKT/mTOR pathway. • Chettaphanin II significantly inhibited the growth of tumor tissue in nude mice. [ABSTRACT FROM AUTHOR]

Terminalia chebula Retz. (T.chebula) is an important medicinal plant in Tibetan medicine and Ayurveda. T.chebula is known as the "King of Tibetan Medicine", due to its widespread clinical pharmacological activity such as anti-inflammatory, antioxidative, antidiabetic as well as anticancer in lots of in vivo and in vitro models. In this study, we use transgenic and/or RNAi Caenorhabditis elegans (C.elegans) model to simulation the AD pathological features induced by Aβ, to detect the effect of TWE on improving Aβ-induced toxicity and the corresponding molecular mechanism. The study aimed to tested the activities and its possible mechanism of T.chebula to against Aβ 1-42 induced toxicity and Aβ 1-42 aggregation. Using transgenic C.elegans strain CL2006 and CL4176 as models respond to paralytic induced by Aβ toxicity. The transcription factors DAF-16 and SKN-1 were analyzed used a fluorescence microscope in transgenic strains (DAF-16:GFP, SKN-1:GFP). The function of DAF-16 and SKN-1 was further investigated using loss-of-function strains by feeding RNA interference (RNAi) bacteria. To evaluate the aggregation level of Aβ in the transgenic C.elegans , Thioflavin S (ThS) staining and WB visualized the levels of Aβ monomers and oligomers. TWE treatment can significantly improve the paralysis of transgenic C.elegans caused by Aβ aggregation (up to 14%). The Aβ aggregates in transgenic C.elegans are significantly inhibited under TWE exposure (up to 70%). TWE increases the nuclear localization of the key transcription factor DAF-16 and HSF-1, which in turn leads to the expression of downstream Hsp-16.2 protein and exerts its inhibitory effect on Aβ aggregation. Meanwhile, paralysis improved has not observed in SKN-1 mutation and/or RNAi C.elegans. Our results indicate that TWE can protect C.elegans against the Aβ 1-42 -induced toxicity, inhibition Aβ 1-42 aggregation and delaying Aβ-induced paralysis. The neuroprotective effect of TWE involves the activation of DAF-16/HSF-1/Hsp-16.2 pathway. Image 1 • The T.chebula water extract (TWE) can delay the paralysis induced by Aβ in transgenic and/or RNA interference C.elegans. • TWE shares protective function via reducing the production of Aβ oligomers. • TWE plays better effect of delaying Aβ-induced paralysis than the ethanol extract. • TWE has the physiological function of cognitive improvement. [ABSTRACT FROM AUTHOR]