Corrigendum: An integrative serum pharmacology-based approach to study the anti-tumor activity of B. Paniculatum aqueous bulb extract on the human hepatocellular carcinoma cell line BEL-7404.

[This corrects the article DOI: 10.3389/fphar.2020.01261.].

Chinese endemic medicinal plant Bolbostemma paniculatum (Maxim.) Franquet: A comprehensive review.

Bolbostemma paniculatum (Maxim.) Franquet is a unique species in China with a long history of medicinal use, which has the effects of detoxifying, dissolving lumps and dispersing swellings. And it is commonly used to treat many diseases, such as carbuncle and sore, acute mastitis, mammary cancer, scrofula and subcutaneous nodule traditionally. Modern clinical studies have found that B. paniculatum and its compounds can be used for the treatment of a variety of cancers, mastitis, hyperplasia of mammary glands, chronic lymphadenitis, cervical lymph tuberculosis and surgical wart skin diseases, and the curative effect is positive. At present, a variety of Chinese patent medicines containing B. paniculatum have been exploited and marketed in China for the treatment of cancers, breast diseases and flat warts. This review article comprehensively discussed the traditional application, botany, chemical components, pharmacological activities, and quality control of B. paniculatum, put forward some noteworthy issues and suggestions in current studies, and briefly discussed the possible development potential of this plant as well as future research perspectives. 96 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids and other components, of which triterpenoid saponins are the main bioactive components. The crude extracts and monomer compounds of B. paniculatum have a wide range of pharmacological activities, such as anti-tumor, antiviral, anti-inflammatory, immunoregulatory, and so on. Moreover, its anti-tumor mechanism involves many aspects, including inhibiting cell proliferation, promoting cell apoptosis, blocking the cell cycle, interfering with cell invasion and metastasis, suppressing angiogenesis, and regulating autophagy. While there is a lack of systematic and in-depth research on its anti-tumor active components and mechanism of action at the moment; and a tight connection between the chemical composition and pharmacological activity of B. paniculatum has also not been established. Besides, a systematic quality determination standard for B. paniculatum should also be built, in order to carry out further research.

Bolbostemma paniculatum (Maxim.) Franquet extract suppresses the development of colorectal cancer through downregulation of PI3K/Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bolbostemma paniculatum (Maxim.) Franquet (BPF), a kind of Chinese medicine, has been traditionally used in treating mastitis, dysentery, phlegm nuclear, and sore swelling poison. AIM OF THE STUDY: In current study, we tried to investigate the possible anti-colorectal cancer (CRC) effects of BPF. MATERIALS AND METHODS: The effects of BPF extract on human colon cancer cells HCT-116 and SW-620, and a colitis associated colorectal cancer (CACC) mouse model were evaluated using the method of experimental pharmacology combined with network pharmacology. RESULTS: The ethyl acetate extract 3 (EA3) of BPF showed the most potent growth inhibitory effect in CRC cells. It could inhibit the clone formation, induce the apoptosis and cell cycle arrest in G1 phase as well as suppress the invasion and migration of CRC cells. And EA3 prevented ICR mice against CACC effectively. Both KEGG and GO analysis indicated that EA3 may inhibit CRC through influencing PI3K/Akt pathway. Results of Western blot analysis and ELISA confirmed that the molecules in the pathway were affected by EA3. CONCLUSIONS: These results demonstrate that EA3 from BPF could suppress the development of CRC through inhibiting the activity of PI3K/Akt pathway.

[Research progress on chemical constituents, pharmacological activities and clinical application of Bolbostemma paniculatum].

Bolbostemma paniculatum is a commonly used Chinese medicinal material effective in clearing heat, removing toxin, eliminating phlegm, and alleviating swelling. The anti-tumor activity it possesses makes it a research hotspot. At present, 76 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids, anthraquinones, organic acids, etc., with anti-tumor, antiviral, and immunosuppressive pharmacological activities. This study reviewed the research on the chemical constituents and pharmacological effects of B. paniculatum over the past 20 years, aiming to provide a scientific basis for the research on the pharmacodynamic material basis and promote the development and utilization of B. paniculatum.

Research progress on chemical constituents, pharmacological activities and clinical application of Bolbostemma paniculatum / 中国中药杂志

Bolbostemma paniculatum is a commonly used Chinese medicinal material effective in clearing heat, removing toxin, eliminating phlegm, and alleviating swelling. The anti-tumor activity it possesses makes it a research hotspot. At present, 76 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids, anthraquinones, organic acids, etc., with anti-tumor, antiviral, and immunosuppressive pharmacological activities. This study reviewed the research on the chemical constituents and pharmacological effects of B. paniculatum over the past 20 years, aiming to provide a scientific basis for the research on the pharmacodynamic material basis and promote the development and utilization of B. paniculatum.

An Integrative Serum Pharmacology-Based Approach to Study the Anti-Tumor Activity of B. paniculatum Aqueous Bulb Extract on the Human Hepatocellular Carcinoma Cell Line BEL-7404.

The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.

Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.

BACKGROUND: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway. METHODS: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used. RESULTS: BPTS inhibited proliferation of MDA-MB-231 cells with an IC50 value of 10 µg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid arthritis using a rat paw edema model.

Smilax glabra Roxb. (Tufuling) and Bolbostemma paniculatum (Maxim.) Franquet (Tubeimu) are used as couplet medicine in traditional Chinese medicine for the treatment of arthritis. This study is conducted to provide evidence on their therapeutic effects on rheumatoid arthritis (RA) and to explore its possible mechanisms of action. The identification and quantification of representative components (Astilbin and Tubeimoside I) in the n-butyl alcohol fraction of this couplet medicine (BFCM) were carried out by HPLC-UV assays. The contents of Astilbin and Tubeimoside I in BFCM were 13.13% (15.434 min) and 3.4% (18.619 min) respectively. For the assessment of anti-RA and anti-inflammatory activities, a carrageenan-induced paw edema model in rats was used. The swelling rates of paws and levels of IL-1ß, IL-6 and TNF-α in the swelling tissue were determined. We observed that the BFCM exhibited significant inhibitory activity on carrageenan-induced paw edema model (p<0.01). The down regulated levels of IL-1ß, IL-6 and TNF-α (all p<0.05) were reported. The results indicate that BFCM possesses significant anti-RA and anti-inflammatory effects, and it has a potential to be developed as a new therapeutic agent against RA.

Rapid Characterization of Components in Bolbostemma paniculatum by UPLC/LTQ-Orbitrap MSn Analysis and Multivariate Statistical Analysis for Herb Discrimination.

Bolbostemma paniculatum is a traditional Chinese medicine (TCM) showed various therapeutic effects. Owing to its complex chemical composition, few investigations have acquired a comprehensive cognition for the chemical profiles of this herb and explicated the differences between samples collected from different places. In this study, a strategy based on UPLC tandem LTQ-Orbitrap MSn was established for characterizing chemical components of B. paniculatum. Through a systematic identification strategy, a total of 60 components in B. paniculatum were rapidly separated in 30 min and identified. Then based on peak intensities of all the characterized components, principle component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to classify 18 batches of B. paniculatum into four groups, which were highly consistent with the four climate types of their original places. And five compounds were finally screened out as chemical markers to discriminate the internal quality of B. paniculatum. As the first study to systematically characterize the chemical components of B. paniculatum by UPLC-MSn, the above results could offer essential data for its pharmacological research. And the current strategy could provide useful reference for future investigations on discovery of important chemical constituents in TCM, as well as establishment of quality control and evaluation method.

Bioassay-guided isolation and identification of cytotoxic compounds from Bolbostemma paniculatum.

ETHNOPHARMACOLOGICAL RELEVANCE: Bolbostemma paniculatum (Maxim.) Franquet (B. paniculatum), also named "Tu-bei-mu" in Chinese folk medicines, has been described in application for the treatment of tumors, warts, inflammation and toxication in traditional Chinese medicinal books. The major constituents in B. paniculatum are triterpenoid saponins, which have been proved to possess dramatically cytotoxic activity and antivirus activity. The aim of this study is to isolate and identify the active triterpenoid saponin from the bulb of B. paniculatum by a bioassay-guided method. MATERIALS AND METHODS: Four cucurbitacine triterpenoid sapogenins and 11 triterpenoid saponins were isolated from the active EtOAc and n-BuOH extract of B. paniculatum by using bioassay-guided screening. Their structures were elucidated based on the spectroscopic methods and compared with published data. Cytotoxic activities of isolated compounds were determined by MTT assay. RESULTS: Four cucurbitacine triterpenoid sapogenins, isocucurbitacin B(1), 23,24-dihydroisocucurbitacin B(2), cucurbitacin E(3), 23,24-dihydrocucurbitacin E(4), and 11 triterpenoid saponins, tubeimosideI(5), tubeimoside III(6), tubeimoside V(7), dexylosyltubeimoside III(8), lobatoside C(9), tubeimoside A(10), tumeimoside B(11), lobatoside A(12), tubeimoside C(13), tubeimoside IV(14), 7ß,18,20,26-tetrahydroxy-(20S)-dammar-24E-en-3-O-α-L-(4-acetyl)arabinopyranosyl-(1→2)-ß-D-glucopyranoside(15) were isolated from the active EtOAc and n-BuOH extracts. Of them, compounds 2, 4, 9 and 12 were firstly isolated from the Bolbostemma genus. MTT assay revealed that compounds 1, 3 and 4 had significantly activities against HeLa and HT-29 human cancer cells with IC50 values ranging from 0.93 to 9.73µM. It is worth mentioning that compound 4׳s activities against the two cell lines are 12- and 8-fold that of the positive control drug (5-Fu). Whereas, the cyclic bisdesmosides 5-9 exerted significantly activities on BGC-823, HeLa, HT-29 and MCF-7 cancer cells with IC50 values ranging from 1.30 to 15.64µM. And 6׳s activities against the four cell lines are 6-, 3-, 10- and 16-fold that of 5-Fu and 8׳s activities against the four cell lines are 5-, 3-, 14- and 9-fold that of 5-Fu. CONCLUSION: The cytotoxic activity of the bulbs of B. paniculatum is mainly ascribable to cucurbitacine triterpenoid sapogenins (1-4) and the cyclic bisdesmosides (5-9). The cyclic bisdesmosides are the main anti-cancer active compounds of B. paniculatum. The above results provide scientific evidence to support, to some extent, the ethnomedicinal use of B. paniculatum as anticancer remedies in traditional Chinese medicine.

Characteristics of ethylcellulose microcapsules containing tubeimoside and its usage in the experimental study of renal arterial chemoembolization / 中华放射学杂志

Objective　To study the efficacy, safety and related characteristics of ethylcellulose microcapsules containing tubeimoside as a vascular embolization agent. Methods　The ethylcellulose microcapsules containing tubeimoside was prepared using tubeimoside from bolbostemma paniculatum of Chinese medicinal herb as the core, and ethylcellulose as the shell. Transcatheter renal arterial embolization was performed with the microcapsules in 30 New Zealand white rabbits. Results　The microcapsules were white, spherical, and smooth particles, with its size to range from 40-180 μm, and its drug content was 36%(W/W); It was divergened best in 40% meglucamine diatrizoate and suspended stably, easily injected through 3 F catheter without occlusion. All of the microcapsules ruptured in about 20 days when immersed in physiological saline at 37℃. The embolized kidneys were smaller than the normal kidneys in weight and volume after 30 days（tw=102.1, tv=38.0, P<0.001）. Serial slices of the kidneys showed that the microcapsules remained mainly at the interlobular artery and the arterial arch, which measured from 110 μm to 350 μm in diameter. The vessels maintained occlusive after 30 days without formation of collateral circulation. Conclusion　Ethylcellulose microcapsules containing tubeimoside were safe and effective with angioembolic function and slow-release. It was a potential peripheral artery embolization agent.