Antiproliferative piperidine alkaloids from the leaves of Alocasia macrorrhiza.

Seventeen piperidine alkaloids, including 15 previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol alkaloids and a previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3-ol alkaloid, were isolated from the leaves of Alocasia macrorrhiza (L.) Schott. Their planar structures and configurations were elucidated based on HR-ESI-MS, 1D and 2D NMR, Snatzke's method, modified Mosher method, single-crystal X-ray crystallography, as well as quantum chemical calculation. It was found that ΔδH5b-H5a can be used to elucidate the relative configuration of 2,3,4,6-tetrasubstituted piperidine, by analyzing the NMR data of 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol. Antiproliferative activity was evaluated for all of the alkaloids, and compounds 6-8 showed considerable inhibitory activity against K562 cell line, with the IC50 values of 17.24 ± 1.62, 19.31 ± 0.9 and 18.77 ± 1.09µM, respectively. Furthermore, compounds 6 and 7 exerted an antiproliferative effect by inducing apoptosis.

Antiproliferative piperidine alkaloids from giant taro (Alocasia macrorrhiza).

The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.

Radioprotective effect of ethanolic extract of Alocasia indica on γ-irradiation-induced reproductive alterations in ovary and uterus.

Evaluation of the modulatory effect of ethanolic extract of Alocasia indica tuber (EEAIT) against γ-irradiation induced ovarian and uterine toxicity. Extract preparation was done by 80% hydro-ethanol using Soxhlet apparatus. EEAIT was administered to female Swiss albino mice (n = 5) daily (200 and 400 mg/kg body weight/d) for 7 days before γ-irradiation exposure (2.9 Gy). FSH, LH, estrogen, progesterone, cytokine levels, and oxidative stress parameters were measured after 24 hours of γ-irradiation. Histology, folliculogenesis, viability of granulosa cells, ROS measurement by flow cytometry, western blot of P450scc, P45017A1, 3ß HSD and SF 1 were also performed. In addition, fertility status was assessed by fecundability and fecundity. The results showed that EEAIT exhibit a strong radioprotective activity by reducing the oxidative stress and thereby restored the ovarian and uterine alterations. EEAIT also improved the abnormality in follicle development, restored altered gonadal hormones and cytokines levels, increase the fertility status, reducing ROS level of granulosa cells with increasing granulosa cells viability and steroidogenic enzyme activity as compared to control. So EEAIT showed a radioprotective effect on γ-irradiation induced ovarian and uterine damage. Our results suggested that Alocasia indica tuber can be a potential radioprotector to prevent female infertility.

In vitro and in vivo anti-malignant melanoma activity of Alocasia cucullata via modulation of the phosphatase and tensin homolog/phosphoinositide 3-kinase/AKT pathway.

Alocasia cucullata, a Chinese herb, has been used as an anticancer treatment in southern China. Phosphatase and tensin (PTEN), is a tumor suppressor gene and the loss of PTEN expression may activate the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway which play a key role in tumors formation and progression. In this study, we evaluated the anti-melanoma effect and the underlying mechanism of 50% ethanolic extract of A. cucullata (EAC) in vitro and in vivo. Using MTT, wound healing, and transwell assays, we found that EAC suppressed the proliferation, migration, and invasion of melanoma cells (B16-F10, A375 and A2058) in a dose-dependent manner. We also found that EAC suppresses B16-F10 tumor growth in a xenografted mouse model. Western blot analysis revealed that the expression level of PTEN was up-regulated, and phosphorylation of PI3K and AKT reduced in B16-F10 cells and tumor tissues after EAC treatment. No significant differences were observed in PI3K and AKT expression. Moreover, immunohistochemistry showed that the number of PTEN-positive cells in tumor tissues increased and that of p-AKT-positive cells decreased with EAC treatment, corroborating the western blot results. Our data reveal that EAC can inhibit malignant melanoma in vitro and in vivo and suggest that its anti-tumor effect is associated with modulation of the PTEN/ PI3K/AKT signaling pathway. In summary, our findings highlight a promising herbal remedy for the treatment of malignant melanoma, which warrants further study.

Piperidine alkaloids from Alocasia macrorrhiza.

Six previously undescribed piperidine alkaloids were isolated from the rhizomes of Alocasia macrorrhiza (L.) Schott. Their structures were elucidated based on 1D and 2D NMR, IR, HR-ESI-MS spectroscopic analysis and the application of a modified Mosher method. All isolated alkaloids were evaluated for cytotoxicity against five human cancer cell lines (CNE-1, Detroit 562, Fadu, MGC-803, and MCF-7) using the MTT method. Only one compound exhibited cytotoxic effects against Detroit 562, Fadu, and MCF-7 cell lines with IC50 values less than 10 µM.

Anti-inflammatory lignanamides and monoindoles from Alocasia macrorrhiza.

Five new lignanamides (1-5), and one new monoindole alkaloid (6), along with eight known compounds (7-14) were isolated and identified from the rhizomes of Alocasia macrorrhiza (giant taro). All purified compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells, and the antiproliferative activities against human nasopharyngeal carcinoma epithelial (CNE-1), human gastric carcinoma (MGC-803), and human breast cancer (MCF-7) cell lines by MTT method. Compounds 2, 4, 7 and 8 exhibited significant inhibitory effects on NO production with the IC50 values of 2.35±0.38, 9.20±0.94, 3.45±0.39 and 7.96±0.56µM, respectively. The results suggested the lignanamides and monoindoles might be responsible for the anti-inflammatory activity of giant taro and might be potential anti-inflammatory candidates.

Cytotoxic constituents of Alocasia macrorrhiza.

An indole alkaloid, 2-(5-hydroxy-1H-indol-3-yl)-2-oxo-acetic acid (1) isolated for the first time from nature, in addition to the nine known compounds 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (2), alocasin B (3), hyrtiosin B (4), α-monopalmitin (5), 1-O-ß-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2(R)-hydroctadecanoyl) amido]-4,8-octadecadiene-1,3-diol (6), 3-epi-betulinic acid (7), 3-epi-ursolic acid (8), ß-sitosterol (9) and ß-sitosterol 3-O-ß-D-glucoside (10) were isolated from the rhizomes of Alocasia macrorrhiza (Araceae). Their structures were elucidated by 1D and 2D NMR spectroscopic data. Of these compounds, 6 exhibited the strongest cytotoxicity against the four tested human cancer cell lines (IC50 of about 10 µM against Hep-2 larynx cancer cells).

The cytotoxic and tyrosine kinase inhibitory properties of C21 steroids and iridoids from the tubers of Alocasia cucullata.

Ten steroids and iridoids were isolated from the tubers of Alocasia cucullata (Lour.) G. Don. Among them, alocasgenin A (1) and alocasgenoside B-C (2-3) were new compounds and the aglycone of compound 1, obtained from the acid hydrolysis of 1, was named alocasgenol (1a). Also, for the first time, tenacigenin B (4), 17ß-tenacigenin-B (5), 3-O-6-deoxy-3-O-methyl-ß-D-allopyranosyl-(1→4)-ß-D-oleandropyranosyl-tenacigenin C (6), marsdenoside A-B (7-8) and tenacigenoside A-B (9-10) were isolated from the genus Alocasia. The chemical structures were elucidated by the extensive analysis of spectral data and compared with the literature. By evaluation of the cytotoxic and tyrosine kinase inhibition, compounds 1-10, 1a and compound 2 showed significant growth inhibition against two tumour cell lines, MGC-803 and HT-29, while compounds 1, 1a, 3, 6 and 8 presented moderate inhibition. Furthermore, compound 2 had the inhibitory property against the enzyme activity biochemically.

Effect of Alocasia indica tuber extract on reducing hepatotoxicity and liver apoptosis in alcohol intoxicated rats.

The possible protective role of ethanolic extract of A. indica tuber (EEAIT) in hepatotoxicity and apoptosis of liver caused by alcohol in rats was investigated. Treatment of rats with alcohol (3 g ethanol per kg body weight per day for 15 days intraperitoneally) produced marked elevation of liver biomarkers such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT), and total bilirubin levels which were reduced by EEAIT in a dose-dependent manner. Furthermore, EEAIT improved antioxidant status (MDA, NO, and GSH) and preserved hepatic cell architecture. Simultaneous supplementation with EEAIT significantly restored hepatic catalase (CAT) and superoxide dismutase (SOD) activity levels towards normal. The studies with biochemical markers were strongly supported by the histopathological evaluation of the liver tissue. EEAIT also attenuated apoptosis and necrosis features of liver cell found in immunohistochemical evaluation. HPLC analysis of the extract showed the presence of three major peaks of which peak 2 (RT: 33.33 min) contains the highest area (%) and UV spectrum analysis identified it as flavonoids. It is therefore suggested that EEAIT can provide a definite protective effect against chronic hepatic injury caused by alcohol in rats, which may mainly be associated with its antioxidative effect.

Alocasia cucullata exhibits strong antitumor effect in vivo by activating antitumor immunity.

Chinese herbal medicines have long been used to treat various illnesses by modulating the human immune response. In this study, we investigate the immuno-modulating effect and antitumor activity of Alocasia Cucullata (AC), a Chinese herb traditionally used to treat infection and cancer. We found that the whole water extract of AC roots could significantly attenuate tumor growth in mouse tumor models. The median survival time of the AC-treated mice was 43 days, 16 days longer than that of the control group. Moreover, the AC-treated mice showed substantially higher induction of key antitumor cytokines, such as IL-2, IFN-γ, and TNF-α, indicating that AC may exert antitumor effect by activating antitumor immunity. To further pinpoint the cellular and molecular mechanism of AC, we studied the dose response of a human monocytic cell line, THP-1, to the whole water extract of AC. Treatment of the AC extract significantly induced THP-1 differentiation into macrophage-like cells and the differentiated THP-1 showed expression of specific macrophage surface markers, such as CD11b and CD14, as well as productions of antitumor cytokines, e.g. IFN-γ and TNF-α. Our data thus point to AC as potentially a new, alternative immuno-modulating herbal remedy for anticancer treatment.

Indole Alkaloids from Alocasia macrorrhiza.

Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.

[Studies on the antitumour effect of Alocasia macrorrhiza].

Models of transplanted tumour in mice and human cancer enograft in nude mice were used to evaluate the antitumour effect of water extract of Alocasia macrorrhiza. Results showed that the inhibitory rate against S180 in mice was 29.38%, and the inhibitory rate against transplantable humman gastroadenitis in nude mice was 51.72%. No antitumour effect was shown against ECA in mice.