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Rice Nutraceuticals and Bioactive Compounds: Extraction, Characterization and Antioxidant Activity: A Review

Zubair M, Anwar F, Arshad I, Malik S, Zafar MN

Comb Chem High Throughput Screen, 2023;26(15):2625-2643.
PMID: 37183472 DOI: 10.2174/1386207326666230512144834

Rice (Oryza sativa L.), a cereal grass, belongs to the genus Oryza from the family Poaceae, which encompasses twenty-five species cultured in many countries of Asia, and partly in the rest of the world. From these species, two viz. Oryza sativa (O. sativa) Asian rice and Oryza glaberrima (O. glaberrima) African rice are commonly found and the most widely consumed staple food by a large part of the human population in the world, especially in Asia due to their nutritional and nutraceutical prospects. Rice, a popular source of carbohydrates, also contains a good amount of dietary fiber, minerals (Ca, Zn, Se, P, K, Mg, Fe, and Mn), protein and vitamin B along with several other medicinally important bioactives such as tocols (α-tocopherols and α-tocotrienols) (ßsitosterol) phenolic acids, flavonoids (apiginine), and oryzanol (24-Methylenecylcoartanyl transferulate). Rice bran is a byproduct of the rice polishing industry and is valuable in terms of containing 15-20% high-value oil. Because of the natural antioxidants present in rice, several medicinal benefits and biological properties can be attributed to rice consumption. The nutrient profile of rice varies based on several factors, such as grains (white, brown, red, and black/purple), the extent of polishing, and the preparation method. Considering the importance of rice as a traditional diet rich in high-value bioactives, together with the existing gap of related information, it is worthwhile to assemble a comprehensive review that focuses on the detailed profile of valuable nutrients and high-value phytochemicals and biological activities of rice to explore its functional food and nutraceutical applications. This review attempts to provide collective information on the essential rice cereal for its nutritional and antioxidant potential.
Fulltext Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA

Chaudhry GE, Akim A, Zafar MN, Abdullah MA, Sung YY, Muhammad TST

J Adv Pharm Technol Res, 2020 07 14;11(3):101-106.
PMID: 33102192 DOI: 10.4103/japtr.JAPTR_26_20

Cancer is a complex multifactorial disease and leading causes of death worldwide. Despite the development of many anticancer drugs, there is a reduced survival rate due to severe side effects. The nontargeted approach of convention drugs is one of the leading players in context to toxicity. Hyaluronan is a versatile bio-polymer and ligand of the receptor (CD44) on cancer cells. The MCF-7 and HT-29 cancer cell lines treated with hyaluronic acid-paclitaxel (HA-PTX) showed the distinguishing morphological features of apoptosis. Flow cytometric analysis showed that HA-PTX induces apoptosis as a significant mode of cell death. The activation level of tumor suppressor protein (p53) increased after PTX treatment in MCF-7, but no changes observed in HT-29 might be due to hereditary mutations. The lack of suppression in AKT and Rho A protein suggest the use of possible inhibitors in future studies which might could play a role in increasing the sensitivity of drug towards mutated cells line and reducing the possibilities for cancer cell survival, migration, and metastasis.
Fulltext Heating effect on quality characteristics of mixed canola cooking oils

Baig A, Zubair M, Sumrra SH, Nazar MF, Zafar MN, Jabeen K, et al.

BMC Chem, 2022 Jan 17;16(1):3.
PMID: 35039092 DOI: 10.1186/s13065-022-00796-z

BACKGROUND: The subcontinent is famous for its variety of seasonal foods cooked in vegetable seed cooking oils at elevated heating. Oils are often of poor quality that effect to consumer health. The work, therefore, planned to examine the effects of heat on the quality of mixed canola cooking oils (MCCOs). MCCOs were analyzed by preparing volatile fatty acid methyl esters (FAMEs) and for physiochemical properties.
RESULTS: A major change was observed in the FAs composition of various MCCOs as coded K-1 to K-5. MCCOs were found rich in unsaturated 9-octadecanoic acid (oleic acid C18:1) and 9, 12-octadecadienoic acid (linoleic acid C18:2) along saturated octadecanoic acid (stearic acid C18:0). Results reveals that canola oil samples are mixed in the range of 4-30% with other vegetable oils and animal fats. The quality of canola cooking oils further reduced after heating to 100 °C, 200 °C and 350 °C, respectively. Quality parameters of MCCOs were significantly altered after heating and found as color (510-520 nm to 570-600 nm), mass 220-237 g to 210-225 g, volume 250 mL to 239 mL, pH (6.76-6.89), specific gravity (0.87-0.92), refractive index (1.471-1.475), saponification value (SV) (0.7-2.5), un-saponifiable matter (2.4-9.8%) and acid value (AV) (1.20-5.0 mg KOH).
CONCLUSION: Heating of oils at elevated temperature have shown a significant effect on pH, specific gravity and un-saponifiable matter (p-value
Metal organic frameworks as promising sensing tools for electrochemical detection of persistent heavy metal ions from water matrices: A concise review

Shafqat SS, Rizwan M, Batool M, Shafqat SR, Mustafa G, Rasheed T, et al.

Chemosphere, 2023 Mar;318:137920.
PMID: 36690256 DOI: 10.1016/j.chemosphere.2023.137920

Water bodies are being polluted rapidly by disposal of toxic chemicals with their huge entrance into drinking water supply chain. Among these pollutants, heavy metal ions (HMIs) are the most challenging one due to their non-biodegradability, toxicity, and ability to biologically hoard in ecological systems, thus posing a foremost danger to human health. This can be addressed by robust, sensitive, selective, and reliable sensing of metal ions which can be achieved by Metal organic frameworks (MOF) based electrochemical sensors. In the present era, MOFs have caught greater interest in a variety of applications including sensing of hazardous pollutants such as heavy metal ions. So, in this review article, types, synthesis and working mechanism of MOF based sensors is explained to give general overview with updated literature. First time, detailed study is done for sensing of metal ions such as chromium, mercury, zinc, copper, manganese, palladium, lead, iron, cadmium and lanthanide by MOFs based electrochemical sensors. The use of MOFs as electrochemical sensors has attractive success story along with some challenges of the area. Considering these challenges, we attempted to highlight the milestone achieved and shortcomings along with future prospective of the MOFs for employing it in electrochemical sensing devices for HMIs. Finally, challenges and future prospects have been discussed to promote the development of MOFs-based sensors in future.
Fulltext Induction of cytotoxicity by Bruguiera gymnorrhiza in human breast carcinoma (MCF-7) cell line via activation of the intrinsic pathway

Chaudhry GE, Rahman NH, Sevakumaran V, Ahmad A, Mohamad H, Zafar MN, et al.

J Adv Pharm Technol Res, 2020 10 10;11(4):233-237.
PMID: 33425710 DOI: 10.4103/japtr.JAPTR_81_20

Breast cancer is among the frequently occurring cancer worldwide. The foremost underline aim of this study was to determine the growth inhibitory effect along with mechanistic study of a Bruguiera gymnorrhiza extract on MCF-7. The cytotoxicity activity was determined by using the MTS assay. Butanol extract exhibited the maximum cytotoxicity activity against the MCF-7 cells with IC50 of 3.39 μg/mL, followed by diethyl ether and methanol extract (IC50 at 16.22 μg/mL and 37.15 μg/mL, respectively) at 72 h. The DeadEndTM Colorimetric Apoptosis Detection System confirmed the induction of apoptosis (via DNA fragmentation) in MCF-7 cells. Both butanol and diethyl ether extracts of B. gymnorrhiza significantly increase the caspase-3 level. However, the diethyl ether extract induced higher caspase-9 levels compared to caspase-8, suggesting that the intrinsic pathway was the major route in the process of apoptosis. Thin-layer chromatography profiling demonstrated the presence of phenolic, terpene, and alkaloid compounds in crude methanol, diethyl ether, and butanol extracts. The phytochemicals present in the extracts of B. gymnorrhiza might have the potential to be a future therapeutic agent against breast cancer.
Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes

Zafar MN, Masood S, Chaudhry GE, Muhammad TST, Dalebrook AF, Nazar MF, et al.

Dalton Trans, 2019 Aug 08.
PMID: 31393494 DOI: 10.1039/c9dt01923e

The two cationic palladium(ii) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(ii) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2-5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2-4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2-5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.
Fulltext Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing

Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, et al.

ACS Omega, 2021 Mar 30;6(12):8210-8225.
PMID: 33817480 DOI: 10.1021/acsomega.0c06242

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.
Fulltext Xylocarpus Moluccensis Induces Cytotoxicity in Human Hepatocellular Carcinoma HepG2 Cell Line via Activation of the Extrinsic Pathway

Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, et al.

Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):17-24.
PMID: 33576208 DOI: 10.31557/APJCP.2021.22.S1.17

OBJECTIVE: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line.
METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.
RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
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Fulltext Induction of Apoptosis by Acanthaster planci sp., and Diadema setosum sp., Fractions in Human Cervical Cancer Cell Line, HeLa

Chaudhry GE, Islamiah M, Zafar MN, Bakar K, Aziz N, Saidin J, et al.

Asian Pac J Cancer Prev, 2021 May 01;22(5):1365-1373.
PMID: 34048163 DOI: 10.31557/APJCP.2021.22.5.1365

Cancer is an uncontrolled multiplication of cells. The desire efficacy and severe toxicity of current anticancer drugs urge exploring and investigating a better alternative to existing chemotherapeutics. Natural products of marine origin are excellent sources of potential new drugs of enhanced biological activities.
OBJECTIVES: Thus, the cytotoxic effects along with investigating the mode of cell death exerted by fractions, AP-9, AP-THR, DS-8 and DS-9 fraction of Acanthaster planci, Diadema setosum sp., on the human cervical cancer cell line, HeLa.
METHODS: The cytotoxicity of fractions has determined by using an MTS assay. The early and late apoptosis was studied by using the High content Screening (HCS) instrument.
RESULTS: The four fractions produced effective cytotoxicity effects with IC50 values at 72hr of less than 20 μg/ml in the order of AP-9 > DS-9 > APTHR-9 > DS-8. The fraction s exhibited cytotoxicity via mediating apoptotic mode of cell death. The early apoptosis by exposure of phosphatidylserine to the outer leaflet of the plasma membrane and late apoptosis due to the presence of green stain (DNA fragmentation) in treated cells.
CONCLUSION: The potent bioactive compounds might be responsible for inducing apoptosis in cancer cells and, thus, the potential to be a successful candidate for exploring upcoming chemotherapeutic drugs.
Fulltext Green photosensitisers for the degradation of selected pesticides of high risk in most susceptible food: A safer approach

Baig A, Zubair M, Sumrra SH, Rashid U, Zafar MN, Ahmad F, et al.

PLoS One, 2021;16(10):e0258864.
PMID: 34710164 DOI: 10.1371/journal.pone.0258864

Pesticides are the leading defence against pests, but their unsafe use reciprocates the pesticide residues in highly susceptible food and is becoming a serious risk for human health. In this study, mint extract and riboflavin were tested as photosensitisers in combination with light irradiation of different frequencies, employed for various time intervals to improve the photo-degradation of deltamethrin (DM) and lambda cyhalothrin (λ-CHT) in cauliflower. Different source of light was studied, either in ultraviolet range (UV-C, 254 nm or UV-A, 320-380 nm) or sunlight simulator (> 380-800 nm). The degradation of the pesticides varied depending on the type of photosensitiser and light source. Photo-degradation of the DM and λ-CHT was enhanced by applying the mint extracts and riboflavin and a more significant degradation was achieved with UV-C than with either UV-A or sunlight, reaching a maximum decrement of the concentration by 67-76%. The light treatments did not significantly affect the in-vitro antioxidant activity of the natural antioxidants in cauliflower. A calculated dietary risk assessment revealed that obvious dietary health hazards of DM and λ-CHT pesticides when sprayed on cauliflower for pest control. The use of green chemical photosensitisers (mint extract and riboflavin) in combination with UV light irradiation represents a novel, sustainable, and safe approach to pesticide reduction in produce.
Pd(II) complexes with chelating N-(1-alkylpyridin-4(1H)-ylidene)amide (PYA) ligands: Synthesis, characterization and evaluation of anticancer activity

Zafar MN, Butt AM, Chaudhry GE, Perveen F, Nazar MF, Masood S, et al.

J Inorg Biochem, 2021 11;224:111590.
PMID: 34507110 DOI: 10.1016/j.jinorgbio.2021.111590

The bidentate N-(1-Alkylpyridin-4(1H)-ylidene)amide (PYA) pro-ligands [H2LBn][Cl]2 (2), and [H2LMe][TfO]2 (3) were prepared by simple alkylation reactions of the known compound, N,N-di(pyridin-4-yl)oxalamide (H2L, 1). The Pd(II) complexes, [Pd(LBn)2][Cl]2 (4), [Pd(LMe)2][Cl][TfO] (5), Pd(LBn)Cl2 (6) and Pd(LMe)Cl2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1-7 revealed that overall 4 and 6 have the largest values for the binding parameters Kb and ΔGbo. The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7, T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4, 6 and 2, respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies.

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