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Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.

Coffee consumption has been associated with many health benefits, that the naturally occurring phytochemicals in coffee are believed to have anti-cancer properties. Unfortunately, established phytochemicals study are scarce. Hence, the present study aimed to evaluate the antioxidant and anti-angiogenic activities of Coffea liberica as influenced by different roasting degrees. Green and roasted (light, medium, dark) Coffea liberica beans were extracted using soxhlet extraction and cold infusion. Preliminary screening showed that roasting did not affect the phytochemicals qualitatively. Light roasted coffee infusion extract had the highest total phenolic content (366.72 ± 1.54 µg/mL) and percentage scavenging; light roasted coffee soxhlet extract had the highest total flavonoid content (324.67 ± 1.19 µg/mL), and green beans soxhlet extract exhibited the highest anti-angiogenic activity with an average score of 1.33. In conclusion, these findings endorse further investigations to determine the active principles and their mode of actions for potential preventative therapies against angiogenesis-related diseases.

Kah Min Yap,1 Mahendran Sekar,1 Lay Jing Seow,1 Siew Hua Gan,2 Srinivasa Reddy Bonam,3 Nur Najihah Izzati Mat Rani,4 Pei Teng Lum,1 Vetriselvan Subramaniyan,5 Yuan Seng Wu,5 Neeraj Kumar Fuloria,6 Shivkanya Fuloria6 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia; 3Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 4Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450, Perak, Malaysia; 5Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 6Faculty of Pharmacy, AIMST University, Kedah, 08100, MalaysiaCorrespondence: Mahendran Sekar Tel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.Keywords: mango, Mangifera indica, mangiferin, breast cancer, molecular mechanism, natural products, women’s health

There is a swing in research developments concerning the utilization of natural products as effective pharmacotherapeutic agents due to their comparatively lower toxicities than synthetic compounds. Among natural products, mangiferin is a natural C-glucosyl xanthonoid polyphenol with remarkable pharmacological activities. Emerging evidence indicates the therapeutic benefits of mangiferin against various kidney disorders, including renal injury, diabetic nephropathy, renal fibrosis, hyperuricemic nephropathy, and lupus nephritis, in experimental animal models. The mangiferin induced antioxidant response resulting in vital functions, such as protection against renal inflammation, inhibits renal cell apoptosis, activates autophagy, causes immunomodulation, regulates renal urate transporters and modulates cell signalling pathways. The purpose of this review provide a brief overview of the in vitro/in vivo reno-protective effect of mangiferin and the underlying mechanism(s) in protecting against kidney disorders. Understanding the pharmacological actions of mangiferin is prominence due to its excellent therapeutic potential in managing kidney disorders. Thus, in addition to this review, in-silico molecular docking is performed against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH) to study the mechanism of action of mangiferin. It is believed that mangiferin is a safe reno-protective molecule. The observed positive effects are attributed to the inhibition of inflammation caused by NF-κB and sEH upregulation and oxidative stress activation. Studies on the efficacy and safety of mangiferin in clinical trials are further warranted to confirm its medicinal potential as therapeutic agent for kidney disorders in humans.

Morinda citrifolia L. has been used for the treatment of a wide variety of diseases, including cancer. This study was undertaken to evaluate the anti-angiogenic effect of M. citrifolia fruits and leaves. Anti-angiogenic activity was evaluated in vivo using the chick chorioallantoic membrane assay. Bioactivity-guided fractionation and isolation were performed to identify the active constituent, and high-performance liquid chromatography analysis was then used to quantify the amount of this active constituent in the active extracts and fraction. The methanol extracts of fruits and leaves of M. citrifolia and the subsequent chloroform fraction of the fruit methanolic extract were found to have potential anti-angiogenic activity and were more potent compared to suramin. Scopoletin was identified as one of the chemical constituents that may be partly responsible for the anti-angiogenic activity of M. citrifolia fruits. The present findings further support the use of M. citrifolia in cancer or other pathological conditions related to angiogenesis.

Ethnopharmacological relevance Gynura segetum is a popular medicinal plant in Indonesia and Malaysia, known to possess various medicinal properties especially for treatment of cancer, diabetes and hypertension. Aim of the study This study was carried out to evaluate the anti-angiogenic effect of Gynura segetum leaves extracts and its fractions. The chemical compositions of the active extracts were also determined. Materials and methods The anti-angiogenic activity of Gynura segetum leaves extracts and its fractions was evaluated in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Gas chromatography–mass spectrometry (GC–MS) analysis was carried out to identify the chemical compositions of the active extracts. Results The CAM treated with Gynura segetum leaves extracts and its fractions (100 μg/disc) showed a significantly greater anti-angiogenic effect compared to the positive control suramin (50 μg/disc). Chemical analysis of the active extracts from the leaves of Gynura segetum yielded nine known compounds: undecane (1), neophytadine (2), hexadecanoic acid, methyl ester (3), 9,12-octadecadienoic acid, methyl ester (4), 9,12,15-octadecatrienoic acid, methyl ester (5), phytol (6), tetradecanal (7), octadecanoic acid, methyl ester (8) and γ-sitosterol (9). Conclusions These results suggested that Gynura segetum has anti-angiogenic activity. The plant may be used as a potential source for protection against cancer.

Three water soluble dicopper(II) complexes, tetrakis(μ-4-chloro-2-nitrobenzoato-κ2O,O′) bis[aquacopper(II)] (1), tetrakis(μ-2-chloro-6-fluorobenzoato-κ2O,O′)bis[aquacopper(II)] (2) and tetrakis(μ-2-chlorobenzoato-κ2O,O′)bis[aquacopper(II)] (3), have been synthesized. Complex 1 crystallizes in monoclinic system, space group C2/c with a = 28.813(3), b = 7.2368(6), c = 17.0053(14) A, β = 105.395° and Z = 4, while 2 crystallizes in triclinic system, space group P 1 ¯ with a = 7.5638(2), b = 13.0494(4), c = 16.7079(5) A, α = 106.003°, β = 90.388°, γ = 91.855° and Z = 2. In addition, all the complexes have been characterized by their elemental analysis, FT-IR, UV–Vis spectroscopy and cyclic voltammetry. All complexes have been found to be redox active displaying two quasi-reversible redox couples corresponding to CuIICuII to CuIICuI and CuIICuI to CuICuI redox processes, respectively. The results from the gel electrophoresis experiment of 1–3 on pBR322 DNA, have demonstrated the occurrence of oxidative cleavage in the presence of hydrogen peroxide. The hydroxyl radical has been found to be the reactive oxygen species that is responsible for the cleavage reaction. In the antiproliferation tests against MCF-7, DU 145, HeLa and HepG2 cancer cell lines, all complexes show significant preference against HepG2 cell lines. All complexes also show significant preference against HepG2 cancer cells line over Chang human normal liver cells which means 1–3 are more potent against cancer cells than normal cells. In antibacterial tests against nine pathogenic bacterial species, all complexes show a very selective trend whereby they exhibit antibacterial activity against the Gram negative bacteria Enterobacter aerogenes.

Gynura segetum, family Compositae, is a cultivated species and can be found growing in the tropical regions of Indonesia and Malaysia. The plant is known for its use for the treatment of cancer, inflammation, diabetes, hypertension and skin afflictions. In the current study, in vivo anti-inflammatory effect of the methanol extract G. segetum leaf and its antioxidant effect in vitro have been investigated for the first time. The in vitro antioxidant activities of the methanol extract were measured using common methods including total phenolic content; total flavonoid content; scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and β-carotene bleaching assays. The in vivo anti-inflammatory activities were tested using the cotton pellet implanted animal model. The measurement of pro-inflammatory cytokine (TNF-α and IL-1) levels in the blood samples of the rats was carried out by using ELISA kits. The inhibitory activity on cyclooxygenase (COX) enzyme of methanol extract was also evaluated. The methanol extract exhibited good antioxidant activity which is associated with their total phenolic and flavonoid contents. Methanol extract strongly inhibited the granuloma tissue formation in rats and the anti-inflammatory potential was mediated through the inhibition of pro-inflammatory cytokines and COX-2 enzyme activities. Taken together, the present study suggests that G. segetum's leaf is a natural source of antioxidants and has potential therapeutic benefits against chronic inflammation.

Purpose: To carry out phytochemical and physicochemical studies on the leaves of Gynura segetum. Methods: Preliminary phytochemical and physicochemical studies using chromatographic techniques,were carried out, Parameters evaluated include ash value, loss on drying and extractive value, amongst others. . Results: Phytochemical results revealed that the leaves of Gynura segetum contain alkaloid, terpene, flavonoid, tannin and saponin. Mean ash value (%) was 13.5 (total), 2.49 (acid-insoluble ash) and 6.14 (water-soluble ash). Loss on drying was 10.70 % while extractive value was 20.60 % in water and 14.13 % in ethanol. Thin layer chromatography (TLC) analysis indicates the presence of rutin in the methanol extract of G. segetum and this was supported by high performance liquid chromatography (HPLC) studies. Conclusion: Useful quantitative and descriptive data essential for identifying and characterizing the plant for the purpose of quality control are presented.

Gynura segetum, family Asteraceae is a cultivated species and can be found growing in the tropical regions of Indonesia and Malaysia. The plant is known for its use for the treatment of cancer, inflammation, diabetes, hypertension and skin afflictions. In the current study, anti-inflammatory effect of Gynura segetum leaf has been investigated. The present study investigated the in vivo anti-inflammatory effect of Gynura segetum leaf by using hen’s egg test-chorioallantoic membrane (HET-CAM) assay. Different solvent extract of Gynura segetum leaf were tested, the most active methanol extract was further fractionated and tested. Among the extracts tested, the methanol extract showed a significant good anti-inflammatory effect (76.8% inhibition at 50 µg/disc) on the HET-CAM assay as compared with the anti-inflammatory drug indomethacin (82.1% inhibition). However, the fractionated sample exhibited a significantly lower activity in comparison to crude methanol extract. The results demonstrated that Gynura segetum leaf displayed remarkable anti-inflammatory effects, which support the folkloric uses of this plant for treatment of inflammation.

Gynura segetum, family Compositae (Asteraceae) is a cultivated species and known to possess various medicinal properties for treatment of cancer, inflammation, diabetes, hypertension and other skin afflictions. The antioxidant activities were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and β-carotene-linoleate model system. The amounts of total phenolic and flavonoid in the extract were also determined. The ethyl acetate fraction consistently exhibited the highest antioxidant activity based on the tests performed. The ethyl acetate fraction was potent at DPPH scavenging activity with the lowest EC50 (91.65ug/ml). Antioxidant activity based on the bleaching rate of β-carotene showed percentage inhibition of 81% comparable to Quercetin (94%) at 250ug/ml. The total phenolic and flavonoid content of ethyl acetate fraction were 214.9ug/ml gallic acid equivalent of extract and 67.5ug/ml quercetin equivalent of extract, respectively. The results of this study suggested the correlation between the antioxidant activity potential and total phenolic and flavonoid contents of the ethyl acetate fraction. Phenolic compounds present in the plants may be a major contributor of antioxidant activities. In conclusion, the ethyl acetate fraction of Gynura segetum’s leaf is a potential source of natural antioxidants with potent antioxidant activities.

Gynura segetum (Lour.) Merr. (Compositae) is a well recognized medicinal plant in Indonesia and Malaysia. It is believed to have an anticoagulant effect and is used in treating snake-bites, inflammations and other skin afflictions. This study was carried out to evaluate the antimicrobial effects of Gynura segetum leaves extracts and its fractions. The chemical compositions of the active extracts were also determined. The antimicrobial activities of different solvent extracts of leaves of Gynura segetum were evaluated using the agar well-diffusion method. The Minimum Inhibitory Concentration (MIC) of the active subfractions was determined by the tube dilution method. Gas Chromatography-mass spectrometry (GC-MS) analysis was carried out to identify the chemical compositions of the active extracts. The ethyl acetate fraction and its subfraction E4 performed potent antimicrobial activities and fifteen known chemical constituents were identified by GCMS analysis as 4-vinylphenol, 1-tetradecene, phenol, 2,4-bis(1,1-dimethylethyl), 1-hexadecene, E-15-heptadecenal, hexadecanoic acid, 1,2-benzenedicarboxylic acid, dibutyl ester, 1-docosene, octadecanoic acid, 1-eicosene, cyclotetracosane, 1,2-benzenedicarboxylic acid, bis(2-ethylhexyl)ester, butanedioic acid, monomethyl ester, niacin and 4-hydroxy-benzoic acid. The results of this study suggested a connection between the antimicrobial activities and the chemical structures. The plant may be used as a potential source for antimicrobial agents.