Bibliometric Analysis of Meningiomas from 2001 to 2023: Focus on the Top 100 Most Cited Papers.

OBJECTIVE: The aim was to conduct a comprehensive bibliometric analysis of meningioma research, focusing on publication trends, top authors, universities, countries, and thematic analysis of keywords. METHODS: From Scopus databases, first we analyzed 23180 papers (or 19,824 articles and 3,356 reviews) published between 2001 and 2023. Second, we selected the top 100 most cited papers and descriptively analyzed on Vosviewer and R Studio (bibliometrix/biblioshiny). RESULTS: For both sets, we highlighted the annual publication trends and the impact of top-cited papers. We identified leading authors, universities, and countries contributing significantly to the field. Keywords analysis categorized research themes across all papers. Specific focus was given to the top 100 most cited documents in meningioma. Details about the annual number of papers, mean citations per year, and the citable years are provided. The top authors are presented by number of publications, citations, h-index, g-index and m-index. Co-words analysis was performed and the main focus of the 100 most cited papers are presented in more than 20 categories CONCLUSION: Our findings may provide insights into the evolution of meningioma research and its scholarly impact. The analysis underscores the pivotal contributions of top authors and institutions, outlines thematic research trends, and highlights areas of significant interest and growth in the field. Our study may contribute to understanding the landscape of meningioma research, guiding future research directions and collaborations.

Cancer research in the United Arab Emirates from birth to present: A bibliometric analysis.

Background: Accumulating evidence indicates that the incidence of cancer is increasing in the United Arab Emirates (UAE). This analysis aimed to determine the current cancer research output in the UAE to guide future national research. Methods: The Scopus database was searched for cancer-related bibliographic data from the UAE. The number of publications, citation analysis, co-authorship of the author, institution, and country, keyword co-occurrence, and reference co-citations were analyzed using the R-studio bibliometrics package and VOSviewer software. Results: A total of 1678 journal articles were retrieved from 1981 to 2022. Cancer research in the UAE (UCR) is increasing at a rate of 14.64% (R-squared = 0.75; F = 46.477; P<0.001). The UAE had a 0.06% participation rate in terms of the number of original articles. The rate of international co-authorship is 40.23%. The U.S.A., U.K., Egypt, Saudi Arabia, India, and Canada had more than 100 co-authored documents from 156 countries that collaborated with the U.A.E. Conclusions: Compared to other nations, the UAE has fewer publications on cancer, although the number is growing. The current report provides an up-to-date and in-depth summary of the trends in UCR. This project is an excellent place for researchers interested in conducting data-mapping work in this field.

Hepatoprotective Effect of Curcumin Nano-Lipid Carrier against Cypermethrin Toxicity by Countering the Oxidative, Inflammatory, and Apoptotic Changes in Wistar Rats.

This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.

Evidence of the gastroprotective and anti- Helicobacter pylori activities of ß-mangostin isolated from Cratoxylum arborescens (vahl) blume.

PURPOSE: ß-Mangostin (BM) from Cratoxylum arborescens demonstrated various pharmacological activities such as anticancer and anti-inflammatory. In this study, we aimed to investigate its antiulcer activity against ethanol ulcer model in rats. MATERIALS AND METHODS: BM was isolated from C. arborescens. Gastric acid output, ulcer index, gross evaluation, mucus production, histological evaluation using hematoxylin and eosin and periodic acid-Schiff staining and immunohistochemical localization for heat shock protein 70 (HSP70) and Bax proteins were investigated. Possible involvement of reduced glutathione, lipid peroxidation, prostaglandin E2, antioxidant enzymes, superoxide dismutase and catalase enzymes, radical scavenging, nonprotein sulfhydryl compounds, and anti-Helicobacter pylori were investigated. RESULTS: BM showed antisecretory activity against the pylorus ligature model. The pretreatment with BM protect gastric mucosa from ethanol damaging effect as seen by the improved gross and histological appearance. BM significantly reduced the ulcer area formation, the submucosal edema, and the leukocytes infiltration compared to the ulcer control. The compound showed intense periodic acid-Schiff staining to the gastric mucus layer and marked amount of alcian blue binding to free gastric mucus. BM significantly increased the gastric homogenate content of prostaglandin E2 glutathione, superoxide dismutase, catalase, and nonprotein sulfhydryl compounds. The compound inhibited the lipid peroxidation revealed by the reduced gastric content of malondialdehyde. Moreover, BM upregulate HSP70 expression and downregulate Bax expression. Furthermore, the compound showed interesting anti-H. pylori activity. CONCLUSION: Thus, it could be concluded that BM possesses gastroprotective activity, which could be attributed to the antisecretory, mucus production, antioxidant, HSP70, antiapoptotic, and anti-H. pylori mechanisms.

Antisecretory, gastroprotective, antioxidant and anti-Helicobcter pylori activity of zerumbone from Zingiber zerumbet (L.) Smith.

BACKGROUND: Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it's locally known among the Malay people as "lempoyang" and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders. AIM OF THE STUDY: The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats. MATERIALS AND METHODS: Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE2), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro. RESULTS: The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p <0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p <0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain. CONCLUSION: The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori.

Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity.

BACKGROUND: Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. METHODS: DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. RESULTS: DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. CONCLUSIONS: The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.

Gastroprotective mechanism of Bauhinia thonningii Schum.

ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia thonningii Schum. (Cesalpiniaceae) is locally known as Tambarib and used to treat various diseases including gastric ulcer. AIM OF THE STUDY: The current study aims to evaluate the gastroprotecive mechanism(s) of methanolic (MEBT) and chloroform (CEBT) extracts of Bauhinia thonningii leaves on ethanol-induced gastric ulceration. MATERIALS AND METHODS: Gastric acidity, quantification and histochemistry of mucus, gross and microscopic examination, nitric oxide, lipid peroxidation, 2D gel electrophoresis, mass spectroscopy and biochemical tests were utilized to assess the mechanism(s) underlying the gastroprotective effects of MEBT and CEBT. Effect of these extracts into lipopolysaccharide/interferon-γ stimulated rodent cells were done in vitro. In vitro and in vivo toxicity studies were also conducted. Antioxidant activities of MEBT and CEBT were examined using DPPH, FRAP and ORAC assays. Phytochemical analyses of MEBT and CEBT were conducted using chemical and spectroscopic methods. RESULTS: Gross and histological features confirmed the anti-ulcerogenic properties of Bauhinia thonningii. Gastroprotective mechanism of MEBT was observed to be mediated through the modulation of PAS-reactive substances, MDA and proteomics biomarkers (creatine kinase, malate dehydrogenase, ATP synthase, actin and thioredoxin). MEBT and CEBT showed no significant in vitro and in vivo effects on nitric oxide. Methanolic extract (MEBT) showed superior gastroprotective effects, polyphenolic content and antioxidant activities compared to CEBT. The plant extracts showed no in vitro or in vivo toxicity. CONCLUSION: It could be concluded that MEBT possesses anti-ulcer activity, which could be attributed to the inhibition of ethanol-induced oxidative damage and the intervention in proteomic pathways but not the nitric oxide pathway.

Dentatin isolated from Clausena excavata induces apoptosis in MCF-7 cells through the intrinsic pathway with involvement of NF-κB signalling and G0/G1 cell cycle arrest: a bioassay-guided approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm. f. has been used in folk medicines in eastern Thailand for the treatment of cancer. MATERIALS AND METHODS: To investigate the apoptosis mechanism, we isolated dentatin (DTN) from this plant using a bioassay-guided approach. DTN-induced cytotoxicity was observed with the MTT assay. Acridine orange/propidium iodide staining was used to detect cells in early apoptosis and high content screening (HCS) to observe nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed with a clonogenic assay, DNA laddering and caspase 3/7 and 9 assays. Reactive oxygen species (ROS) formation, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. The involvement of nuclear factor-kappa B (NF-κB) was analysed with the HCS assay. RESULTS: A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Apoptosis was confirmed by the reduced number of colonies in the clonogenic assay and the increased number of cellular DNA breaks in treated cells observed as a DNA ladder. Treatment of MCF-7 cells with DTN encouraged apoptosis with cell death-transducing signals that reduced MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase 9 followed by the executioner caspase 3/7. DTN treatment significantly arrested MCF-7 cells at the G0/G1 phase (p<0.05) and ROS was significantly elevated. Moreover, DTN significantly blocked the induced translocation of NF-κB from cytoplasm to nucleus. CONCLUSION: Together, the results demonstrated that the DTN isolated from Clausena excavata inhibited the proliferation of MCF-7 cells, leading to cell cycle arrest and programmed cell death, which was confirmed to occur through the mitochondrial pathway with involvement of the NF-κB signalling pathway.

Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A.

The plant Artocarpus obtusus is a tropical plant that belongs to the family Moraceae. In the present study a xanthone compound Pyranocycloartobiloxanthone A (PA) was isolated from this plant and the apoptosis mechanism was investigated. PA induced cytotoxicity was observed using MTT assay. High content screening (HCS) was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Reactive oxygen species formation was investigated on treated cells by using fluorescent analysis. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition mRNA levels of Bax and Bcl2 were also checked using RT-PCR. Caspase 3/7, 8 and 9 were measured for their induction while treatment. The involvement of NF-κB was analyzed using HCS assay. The results showed that PA possesses the characteristics of selectively inducing cell death of tumor cells as no inhibition was observed in non-tumorigenic cells even at 30 µg/ml. Treatment of MCF7 cells with PA induced apoptosis with cell death-transducing signals, that regulate the MMP by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of cytochrome c triggered the activation of caspases-9, then activates downstream executioner caspase-3/7 and consequently cleaved specific substrates leading to apoptotic changes. This form of apoptosis was found closely associated with the extrinsic pathway caspase (caspase-8) and inhibition of translocation of NF-κB from cytoplasm to nucleus. The results demonstrated that PA induced apoptosis of MCF7 cells through NF-κB and Bcl2/Bax signaling pathways with the involvement of caspases.

Gastroprotective activities of Turnera diffusa Willd. ex Schult. revisited: Role of arbutin.

ETHNOPHARMACOLOGICAL RELEVANCE: Turnera diffusa Willd. ex Schult. has been used for the treatment of several human disorders including peptic ulcer. OBJECTIVES OF THE STUDY: The current study is an attempt to evaluate the anti-ulcerogenic activities of arbutin, a major constituent of Turnera diffusa on two ulcer models. The possible involvement of lipid peroxidation, nitric oxide, IL-6, IL-10, TNF-α and mucus barrier mechanism has been investigated. MATERIALS AND METHODS: Effects of arbutin on ulcer index, gastric juice acidity, mucus content and histochemistry, gross and histological gastric lesions, nitric oxide, cytokines levels (IL-6, IL-10 and TNF-α), and thiobarbituric acid reactive substances (TBARS), were evaluated in aspirin or ethanol-induced ulcer in vivo. Acute toxicity of arbutin was also examined in rodent model. MTT assay was used to assess the cytotoxicity of the compound on normal liver cells (WRL-68). RESULTS: Pre-treatment with arbutin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of edema, inflammation and leucocytes infiltration on both models. Arbutin significantly (P<0.05) lowered the elevated TBARS level into gasteric homogenate. Arbutin did not produce significant inhibition of NO. This natural compound has modulated the levels of interleukin-6, interleukin-10 and TNF-α. No in vitro or in vivo toxicities for arbutin were observed. CONCLUSION: Thus it can be concluded that Turnera diffusa possesses anti-ulcer activity, which could be attributed to lipid peroxidation inhibitory, immuno modulatory and anti-oxidant mechanisms of arbutin but not to the intervention with nitric oxide inflammation pathway.

The methanolic extract of Boesenbergia rotunda (L.) Mansf. and its major compound pinostrobin induces anti-ulcerogenic property in vivo: possible involvement of indirect antioxidant action.

ETHNOPHARMACOLOGICAL RELEVANCE: Boesenbergia rotunda (L) Mansf. has been used for the treatment of gastrointestinal disorders including peptic ulcer. In the current study we aimed to investiagte the anti-ulcer activities of methanolic extract of B. rotunda (MEBR) and its main active compound, pinostrobin on ethanol-induced ulcer in rats. The possible involevement of lipid peroxidation, nitric oxide, cyclooxygenases and free radical scavenging mechanisms also has been investigated. MATERIALS AND METHODS: Pinostrobin was isolated form the rhizomes of B. rotunda. Ulcer index, gastric juice acidity, mucus content, gross and histological gastric lesions and thiobarbituric acid reactive substances (TBARS) were evaluated in ethanol-induced ulcer in vivo. The effect of pinostrobin into lipopolysaccharide/interferon-γ stimulated rodent cells, COX-1 and COX-2 activities were done in vitro. RESULTS: Pre-treatment with MEBR, pinostrobin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of submucosal edema and leucocytes infiltration. Pinostrobin significantly (p<0.05) lowered the elevated TBARS level into gasteric homogenate. Pinostrobin did not produced significant in vitro inhibition of NO from LPS/IFN-γ activated rodent cells without affecting the viability of these cells. Further, the compound did bot revleaed inhibitory effects on both COX- 1& 2 enzymes. The antioxidant assays also exhibited non significance in vitro. CONCLUSION: Thus it can be concluded that MEBR possesses anti-ulcer activity, which could be attributed to indirect anti-oxidant mechanism of pinostrobin but not to the intervention with nitric oxide and COX inflammation pathways.

Zerumbone induces apoptosis in T-acute lymphoblastic leukemia cells.

Zerumbone (ZER) is a potential anticancer natural compound, isolated from Zingiber zerumbet Smith. In this investigation, the anticancer properties of ZER were evaluated on cancer cells of T-acute lymphoblastic leukemia, CEM-ss. The results showed that ZER has cytotoxic effect against CEM-ss cells with an IC(50) of 8.4 ± 1.9 µg/ml (coefficient of variation < 30%). Comparatively, 5-fluorouracil (positive control), imposed an inhibitory effect on CEM-ss cells with an IC(50) of 1.94 ± 0.06 µg/ml. Scanning electron microscopy (SEM) results revealed abnormalities such as membrane blebbing, holes and cytoplasmic extrusions, all of which are characteristics of apoptosis. In addition, ZER has increased the number of TUNEL-positive stain and the cellular level of caspase-3, the hallmarks of apoptosis, on treated CEM-ss cells. It could be concluded that, ZER was able to produce apoptosis on T-acute lymphoblastic leukemia, CEM-ss. The current findings suggest that ZER might be helpful for improving the usefulness of anticancer agents in the therapy of leukemia.

Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo.

Typhonium flagelliforme (TF) is a tropical plant, traditionally used by the ethnic population of Malaysia for the cure of various cancers. This plant had shown to induce antiproliferative effect as well as apoptosis in cancer cells. However, there is no available information to address that TF affects murine leukemia cells in vitro and in vivo. Here, we investigated in vitro and in vivo effects of TF on murine leukemia WEHI-3 cells. It was found that the growth of leukemia cells in vitro was inhibited by the various extracts of TF. Among these fractions, the dichloromethane (DCM) tuber extracts of TF showed the lowest IC(50) (24.0 ± 5.2 µg/ml) and had demonstrated apoptogenic effect when observed under fluorescent microscope. We investigated the in vivo effects of DCM tuber extracts of TF on murine leukemia cells, and the results showed that the counts of immature granulocytes and monocytes were significantly decreased in peripheral blood of BALB/c leukemia mice after the oral administration of DCM tuber extracts of TF for 28 days with three doses (200, 400 and 800 mg/kg). These results were confirmed by observing the spleen histopathology and morphology of enlarged spleen and liver in leukemia mice when compared with the control. Furthermore, the cell death mechanism in the spleen tissue of treated mice was found via apoptosis.

Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet).

Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P<0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P<0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P<0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P<0.05) lowered. By the TUNEL assay, there were significantly (P<0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.

Combination of zerumbone and cisplatin to treat cervical intraepithelial neoplasia in female BALB/c mice.

Recent in vitro and in vivo studies have demonstrated that zerumbone (ZER) possesses anticancer properties. The main objective of this study was to examine the effectiveness of the combination of ZER and cisplatin (CIS) to treat cervical intraepithelial neoplasia (CIN) in vivo. Microculture tetrazolium assay and immunohistochemistry of proliferating cellular nuclear antigen were used to study the antitumor effect of ZER. Prenatally exposed female BALB/c mice were used as a model. The progenies with CIN were injected peritoneally with isotonic sodium chloride solution (positive control), CIS, ZER, and a combination of both compounds. All treated and untreated mice were humanely killed, and serum and cervix were obtained for interleukin 6 analysis and histopathologic studies using hematoxylin and eosin staining, respectively. Zerumbone has revealed an antitumor effect on human cervical cancer cells and downregulates immunoexpression of proliferating cellular nuclear antigen (P < 0.05). In vivo study indicates that ZER at 16 mg/kg and CIS at 10 mg/kg have a regressing effect on CIN. The combination of ZER and CIS also showed similar effectiveness in regressing CIN. Our results indicate that the combination of ZER and CIS has modulated the serum level of interleukin 6 when compared with that in mice treated with isotonic sodium chloride solution (P < 0.05). The effectiveness of combining ZER and CIS could be further explored as a new therapeutic intervention of early precancerous stages of carcinogenesis before the invasive stage begins.