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Numerous attempts have been made to control leptospirosis by using chemoprophylaxis, but with limited success. The present study was done to investigate the antileptospiral potential of hexane, ethyl acetate and methanol extracts of Zingiber zerumbet rhizomes. The extracts were assayed for antileptospiral activity using broth microdilution method against Leptospira interrogans (serovar Batavie, Canicola, Australis) and Leptospira biflexa serovar Patoc. The Z. zerumbet hexane extract exhibited antileptospiral activity, with IC50 values of 248 μg/mL against L. interrogans serovar Canicola, IC50 of 125 μg/mL against L. interrogans serovar Australis, IC50 of 15.63 μg/mL against L. interrogans serovar Batavie and IC50 of 109 μg/mL against L. biflexa serovar Patoc. However, both ethyl acetate and methanol extracts did not show any distinct antileptospiral activity. Since the hexane extract of Z. zerumbet showed antileptospiral activity, the DNA-damaging properties of this extract were tested according to their IC50 and IC25 values that were specific to each serovars. The DNA-damaging properties were determined by treating the selected Leptospira spp. with the hexane extract and subjecting its DNA to electrophoresis and analysis on agarose gels. The results demonstrated that the hexane extract had DNA-damaging properties towards L. biflexa serovar Patoc and L. interrogans serovar Australis, as proven by the appearance of fragmented DNA on the gels. We conclude that the Z. zerumbet hexane extract could inhibit the growth of Leptospira spp. serovar Patoc and Australis through DNA-damaging activity and thus, could be a potential antileptospiral agent. Further studies are needed to investigate the potential of this hexane extract as an antileptospiral agent using in vivo rat models of leptospirosis.

Autofagi adalah proses fisiologi yang terlibat dalam penggantian komponen sel dan berfungsi sebagai mekanisme kelangsungan hidup sementara semasa kebuluran sel akibat kekurangan sumber makanan. Proses ini melibatkan tapak jalan lisosom yang menguraikan bahan yang terdapat dalam sitoplasma seperti organel dan makromolekul. Keberlangsungan proses autofagi bergantung kepada fungsi normal lisosom untuk mengurai dan mengitar semula bahan yang terkumpul di dalam autofagosom. Kegagalan fungsi pada lisosom akan mempengaruhi fungsi autofagi. Secara in vitro, proses autofagi boleh direncat dengan menggunakan bahan kimia seperti amonium klorida yang akan mengganggu fungsi lisosom melalui peningkatan pH lisosom yang seterusnya menghalang keberkesanan enzim lisosom. Hal ini akan menyebabkan kandungan di dalam autofagosom tidak dapat diurai dan meningkatkan penimbunan autofagosom yang mengandungi protein yang rosak. Penimbunan protein yang rosak ini telah dikenal pasti sebagai salah satu patogenesis penyakit neurodegenerasi yang kini dikaitkan dengan ketidakfungsian sel endotelium di otak. Perencatan tapak jalan autofagi-lisosom ini akan menyebabkan gangguan pembentukan struktur autofagi dan lisosom yang seterusnya menyebabkan peningkatan atau penurunan ekspresi protein seperti LC3 dan p62 yang terlibat dalam tapak jalan ini. ICAM-1, eNOS dan Claudin-5 pada sel endotelium merupakan antara penanda yang berpotensi digunakan dalam pengenalpastian ketidakfungsian yang mungkin berlaku pada sel endotelium otak manusia.

Cancer is one of the main causes of mortality in the world. New compounds are currently being synthesized to overcome this disease. Organotin is getting more attention as anticancer agent due to its potent cytotoxic properties towards cancer cells. In this study, a series of newly synthesized organotin compounds known as dimethyltin(IV) (compound 1), dibutyltin(IV) (compound 2) and triphenyltin(IV)methylisoprophyldithiocarbamate (compound 3) have been assessed for their cytotoxic effect towards leukemic cell line K-562. MTT [3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide] assay was employed to determine the cytotoxic effect for each of the compounds at different time points and concentrations. Compound 2 and 3 exhibited potent cytotoxic effects towards K-562 cells with IC50 values less than 2 µM. Compound 3 was found as the most toxic towards K-562 cells based on the lowest IC50 value for 72 h period of treatment at 0.25 µM. Morphological observation was conducted with IC50 values at 24, 48, and 72 h. Results showed that the changes were first observed as early as 24 h and the most significant changes were observed after 72 h period of treatment with the characteristic of apoptosis such as cell shrinkage and membrane blebbing. In addition, necrosis characteristic such as cell lysis and swelling had also been observed. Organotin(IV) methylisopropyldithiocarbamate with different functional groups affect the cytotoxic properties towards leukemic cells K-562 and these compounds have potential to be developed as an anticancer agent through structural modification.

Cisplatin is a chemotherapeutic agent widely used in treating various types of cancer. However, its usage is restricted due to the adverse hepatoxicity, as seen in approximately 36% of cancer patients receiving cisplatin treatment. Polygonum minus essential oil has high antioxidant capacity, and is enriched with terpenoids and phenolic compounds. The objective of this study was to investigate effects of P. minus essential oil (PmEO) supplementation on cisplatin-induced hepatotoxicity in rats. Male rats were divided into seven different groups, namely: control (C), cisplatin-induced (CP), positive control with β-caryophyllene 150 mg/kg (BCP), PmEO 100 mg/kg (PmEO100CP), PmEO 200 mg/kg (PmEO200CP), PmEO 400 mg/kg (PmEO400CP) and PmEO 400 mg/kg alone (PmEO400). PmEO and BCP was given orally for 14 days prior to a single dose cisplatin (10 mg/kg) injection on day 15 and rats were sacrificed on day 18. Liver enzymes, histology, ultrastructural morphology and oxidative stress markers such as glutathione, glutathione peroxidase, catalase, superoxide dismutase and malondialdehyde were assayed. Compared to controls, levels of transaminase enzymes, serum bilirubin and oxidative stress were all increased in CP, PmEO200CP and PmEO400CP groups. However, only PmEO100CP and BCP groups reduced these increases in level of transaminase enzymes and oxidative stress compared to CP group. On both light microscopic and ultrastructural examination, CP and PmEO400CP groups showed hepatotoxicity, exhibited by cytoplasmic vacuolation, congested blood sinusoids and increased number of Kupffer cells. However, these changes were minimized in the PmEO100CP group. Therefore, we concluded that PmEO given at 100 mg/kg has preventive effect against cisplatin-induced hepatotoxicity in rats.

Zingiber zerumbet is widely used as therapeutic agent in traditional medicine and is reported to exert antioxidant activities. This study evaluated in vitro antioxidant potential of Z. zerumbet rhizome ethyl acetate extract on hydrogen peroxide (H2O2)-induced red blood cells (RBCs) damage; by measuring percentage of haemolysis, oxidative damage and morphological changes in treated RBCs. On a preliminary dose-response analysis, it was observed that incubation of RBCs with extract at doses of 50, 25, 12.5 and 6.25 μg/mL all had no significant effect on RBCs similar to NaCl control and BHT (positive control), therefore, these concentrations were used in the subsequent study. The RBCs were pre-incubated with extract in the chosen concentrations, prior to treatment with H2O2. The results showed that only 6.25 μg/mL+H2O2 group showed significantly (p

Zingiber zerumbet is a plant that is traditionally consumed in many countries, including Malaysia due to its therapeutic properties. Previously it has been proven to inhibit migration and proliferation of cancer cells. However, its effects on normal cells are still unknown and would be the main focus of this study. The cytotoxicity along with proliferation and migration activities were evaluated against human dermal fibroblast adult cell line (HDF-a) using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium], proliferation and scratch assays. The cytotoxicity effect was determined following 24 h of treatment by ethyl acetate Z. zerumbet extracts while proliferation assay was conducted at different concentrations (500, 750, 1000, 1250 and 1500 μg/mL) at 24, 48 and 72 h. The cell migration rate was determined by scratch assay in 6-well culture plate using 10 μL pipette tip following 80% confluency at optimum concentration (750 μg/mL) of Z. zerumbet at different time points. Migration rate was scored at every 24 h using digital camera connected to the inverted microscope. The results from cytotoxicity test showed no IC50 values were observed for Z. zerumbet extract as compared to the positive control (menadione). Proliferation assay exhibited highest cell viability (137%) at 750 μg/mL. The rate of cell migration increased following treatment with Z. zerumbet extract after 48 h. However, the result was not significantly different when compared to the control. In conclusion, Z. zerumbet ethyl acetate extract is able to induce cell proliferation and potentially promoting migration rate of wound healing in in-vitro model.

Zingiber zerumbet has been traditionally used as an anti-inflammation and antioxidant agent. The present study investigates the neuroprotective effects of ethyl acetate extract of Z. zerumbet against oxidative stress on paraquat (PQ)-induced Parkinsonism in rats. Forty male Sprague-Dawley rats were divided into five groups: Negative control (normal saline), positive control (N-acetylcysteine, NAC 20 mg/kg + PQ 10 mg/kg), PQ only, 200 mg/kg Z. zerumbet + PQ and 400 mg/kg Z. zerumbet + PQ. The extract was given orally for 19 consecutive days and PQ was administered intraperitoneally on day 8-12th of the treatment regime. Both serum and fresh brains containing substantia nigra (SN) region were taken for biochemical and histological analysis. Administration of both 200 and 400 mg/kg ethyl acetate Z. zerumbet extracts to the PQ-treated groups have resulted in: Decreased levels of MDA and PC in the SN homogenates; and increased SOD, GPx; and CAT activities in the SN and serum. Overall, ethyl acetate extract of Z. zerumbet reduced oxidative stress in the SN of PQ-induced neuronal damages, therefore, has the potential to be developed as a preventive agent for neurodegenerative disorders caused by environmental toxins.