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  1. Mohd Ariffin NH, Hasham R
    Heliyon, 2020 May;6(5):e03955.
    PMID: 32478187 DOI: 10.1016/j.heliyon.2020.e03955
    Skin is the largest external organ of the human body. It acts as a barrier to protect the human body from environmental pollution, mechanical stress, and excessive water loss. The defensive function resides primarily on top of the epidermis layer commonly known as stratum corneum (SC). Human SC consists of three major lipids, namely ceramide, free fatty acid, and cholesterol that comprise approximately 50%, 25%, and 25% of the total lipid mass, respectively. The optimal composition of SC lipids is the vital epidermal barrier function of the skin. On the other hand, skin barrier serves to limit passive water loss from the body, reduces chemical absorption from the environment, and prevents microbial infection. In contrast, epidermal lipids are important to maintain the cell structure, growth and differentiation, cohesion and desquamation as well as formation of a permeability barrier. Multiple non-invasive in vivo approaches were implemented on a regular basis to monitor skin physiological and intercellular lipid properties. The measurement of different parameters such as transepidermal water loss (TEWL), hydration level, skin elasticity, collagen intensity, melanin content, sebum, pH, and tape stripping is essential to evaluate the epidermal barrier function. Novel non-invasive techniques such as tape stripping, ultrasound imaging, and laser confocal microscopy offer higher possibility of accurate and detailed characterisation of skin barrier. To date, these techniques have also been widely used to determine the effects of herbal plants in dermatology. Herbal plants have been traditionally used for ages to treat a variety of skin diseases, as reported by the World Health Organisation (WHO). Their availability, lower cost, and minimal or no side effects have created awareness among society, thus increase the demand for natural sources as the remedy to treat various skin diseases. This paper reviews several non-invasive techniques and evaluations of herbal-based product in dermatology.
  2. Idris MKH, Hasham R, Ismail HF
    Daru, 2022 Dec;30(2):253-272.
    PMID: 35922691 DOI: 10.1007/s40199-021-00414-8
    BACKGROUND: Metabolic syndrome (MetS) is a risk factor for prostate cancer (PCa) progression. Thus, this life-threatening disease demands a proactive treatment strategy. Andrographis paniculata (AP) is a promising candidate with various medicinal properties. However, the bioactivity of AP is influenced by its processing conditions especially the extraction solvent.

    OBJECTIVE: In the present study, bioassay-guided screening technique was employed to identify the best AP extract in the management of MetS, PCa, and MetS-PCa co-disease in vitro.

    METHODS: Five AP extracts by different solvent systems; APE1 (aqueous), APE2 (absolute methanol), APE3 (absolute ethanol), APE4 (40% methanol), and APE5 (60% ethanol) were screened through their phytochemical profile, in-vitro anti-cancer, anti-obese, and anti-hyperglycemic properties. The best extract was further tested for its potential in MetS-induced PCa progression.

    RESULTS: APE2 contained the highest andrographolide (1.34 ± 0.05 mg/mL) and total phenolic content (8.85 ± 0.63 GAE/gDW). However, APE3 has the highest flavonoid content (11.52 ± 0.80 RE/gDW). APE2 was also a good scavenger of DPPH radicals (EC50 = 397.0 µg/mL). In cell-based assays, among all extracts, APE2 exhibited the highest antiproliferative activity (IC50 = 57.5 ± 11.8 µg/mL) on DU145 cancer cell line as well as on its migration activity. In in-vitro anti-obese study, all extracts significantly reduced lipid formation in 3T3-L1 cells. The highest insulin-sensitizing and -mimicking actions were exerted by both APE2 and APE3. Taken together, APE2 showed collectively good activity in the inhibition of PCa progression and MetS manifestation in vitro, compared to other extracts. Therefore, APE2 was further investigated for its potential to intervene DU145 progression induced with leptin (10-100 ng/mL) and adipocyte conditioned media (CM) (10% v/v). Interestingly, APE2 significantly diminished the progression of the cancer cell that has been pre-treated with leptin and CM through cell cycle arrest at S phase and induction of cell death.

    CONCLUSION: In conclusion, AP extracts rich with andrographolide has the potential to be used as an alternative to ameliorate PCa progression induced by factors highly expressed in MetS.

  3. Rabiu Z, Hamzah MAAM, Hasham R, Zakaria ZA
    Environ Sci Pollut Res Int, 2021 Aug;28(30):40535-40543.
    PMID: 32418105 DOI: 10.1007/s11356-020-09209-x
    Pyroligneous acid (PA) obtained from slow pyrolysis of palm kernel shell (PKS) has high total phenolic contents and exhibits various biological activities including antioxidant, antibacterial and antifungal. In this study, PA obtained using slow pyrolysis method and fractionated using column chromatography was characterized (chemical and antioxidative properties) and investigated for its cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibition activities using the in vitro and in silico approaches. The F9 PA fraction exhibited highest total phenolic content of 181.75 ± 17.0 μg/mL. Fraction F21-25 showed ferric reducing antioxidant power (FRAP) (331.80 ± 4.60 mg TE/g) and IC50 of 18.56 ± 0.01 μg/mL towards COX-2 and 5.25 ± 0.03 μg/mL towards the 5-LOX enzymes, respectively. Molecular docking analysis suggested favourable binding energy for all chemical compounds present in fraction F21-25, notably 1-(2,4,6-trihydroxyphenyl)-2-pentanone, towards both COX-2 (- 6.9 kcal/mol) and 5-LOX (- 6.4 kcal/mol) enzymes. As a conclusion, PA from PKS has the potential to be used as an alternative antioxidant and antiinflammatory agents which is biodegradable and a more sustainable supply of raw materials.
  4. Ariffin NHM, Hasham R, Hamzah MAAM, Park CS
    Fitoterapia, 2024 Jan;172:105755.
    PMID: 38000761 DOI: 10.1016/j.fitote.2023.105755
    Ficus deltoidea was known for its potent antioxidant, anti-melanogenic and photoprotective skin barrier activities. These properties are contributed by its biomarkers which are vitexin and isovitexin. This study aims to optimize the yield of methanolic extraction of Ficus deltoidea leaves (EFD) and evaluate their effects on skin barrier function and hydration. For optimization, Box-Behnken design was utilized to investigate the effects of methanol concentration, sonication time, and solvent-to-sample ratio on the yields of vitexin and isovitexin in EFD. The optimal yields obtained were 32.29 mg/g for vitexin and 35.87 mg/g for isovitexin. The optimum extraction conditions were 77.66% methanol concentration, 20.03 min sonication time, and 19.88 mL/g solvent-to-sample ratio. The quantitative real-time polymerase chain reaction was utilized to measure variant marker genes of transglutaminase-1, caspase 14, ceramide synthase 3, involucrin, and filaggrin of EFD-induced keratinocyte differentiation by in vitro study. Exposure to EFD has elevated the mRNA levels of all tested marker genes by 0.7-9.2 folds. Then, in vivo efficacy study was conducted on 20 female subjects for 14 days to evaluate skin biophysical assessment of hydration. EFD topical formulation treatment successfully increased skin hydration on day 7 (43.74%) and day 14 (47.23%). In silico study by molecular docking was performed to identify intermolecular binding interactions of vitexin and isovitexin with the interested proteins of tested marker genes. The result of molecular docking to the interested proteins revealed a similar trend with real-time PCR data. In conclusion, EFD potentially enhanced the skin barrier function and hydration of human skin cells.
  5. Abd Aziz NA, Hasham R, Sarmidi MR, Suhaimi SH, Idris MKH
    Saudi Pharm J, 2021 Feb;29(2):143-165.
    PMID: 33679177 DOI: 10.1016/j.jsps.2020.12.016
    Medicinal plants have gained much interest in the prevention and treatment of common human disease such as cold and fever, hypertension and postpartum. Bioactive compounds from medicinal plants were synthesised using effective extraction methods which have important roles in the pharmaceutical product development. Orthosiphon aristatus (OA), Eurycoma longifolia (EL) and Andrographis paniculata (AP) are among popular medicinal herbs in Southeast Asia. The major compounds for these medicinal plants are polar bioactive compounds (rosmarinic acid, eurycomanone and andrographolide) which have multiple benefits to human health. The bioactive compounds are used as a drug to function against a variety of diseases with the support of scientific evidence. This paper was intended to prepare a complete review about the extraction techniques (e.g. OA, EL and AP) of these medicinal plants based on existing studies and scientific works. Suitable solvents and techniques to obtain their major bioactive compounds and their therapeutic potentials were discussed.
  6. Tarmizi AAA, Wagiran A, Mohd Salleh F, Chua LS, Abdullah FI, Hasham R, et al.
    Plants (Basel), 2021 Apr 07;10(4).
    PMID: 33917172 DOI: 10.3390/plants10040717
    Labisia pumila is a precious herb in Southeast Asia that is traditionally used as a health supplement and has been extensively commercialized due to its claimed therapeutic properties in boosting a healthy female reproductive system. Indigenous people used these plants by boiling the leaves; however, in recent years it has been marketed as powdered or capsuled products. Accordingly, accuracy in determination of the authenticity of these modern herbal products has faced great challenges. Lack of authenticity is a public health risk because incorrectly used herbal species can cause adverse effects. Hence, any measures that may aid product authentication would be beneficial. Given the widespread use of Labisia herbal products, the current study focuses on authenticity testing via an integral approach of DNA barcoding and qualitative analysis using HPLC. This study successfully generated DNA reference barcodes (ITS2 and rbcL) for L. pumila var. alata and pumila. The DNA barcode that was generated was then used to identify species of Labisia pumila in herbal medicinal products, while HPLC was utilized to determine their quality. The findings through the synergistic approach (DNA barcode and HPLC) implemented in this study indicate the importance of both methods in providing the strong evidence required for the identification of true species and to examine the authenticity of such herbal medicinal products.
  7. Adli SA, Ali F, Azmi AS, Anuar H, Nasir NAM, Hasham R, et al.
    Polymers (Basel), 2020 Jul 27;12(8).
    PMID: 32727165 DOI: 10.3390/polym12081669
    The usage of non-degradable polymer as the main matrix for a cosmetic patch raises concern, as it can cause environmental pollution when discarded in landfill. Thus, biodegradable polylactic acid (PLA) was chosen in this study, as PLA has non-toxic properties and similar mechanical properties to conventional plastic materials. An active ingredient in a cosmetic patch serves the purpose of providing beneficial ingredients to the skin; therefore, phycocyanin, an extract from spirulina, was chosen, as it possesses antioxidant and anti-inflammatory properties. Alginate was also incorporated with the phycocyanin for fabrication onto the PLA matrix. A preliminary study was first carried out to identify the antioxidant properties and cytotoxic effect of the phycocyanin on skin cells. It was observed that phycocyanin had no cytotoxic effect on the skin and showed good antioxidant activity. PLA/phycocyanin-alginate composite was fabricated using a solvent casting method, and optimization of preparation conditions (phycocyanin/alginate ratio, stirring time, and temperature) were carried out using the one-factor-at-a-time (OFAT) method with responses of elongation at break and releasing properties. Attenuated total reflectance (ATR)-FTIR analysis was also conducted to further analyze the functional group of the composites. Surface morphologies were observed for samples before and after the releasing test. From the analyses conducted, PLA/phycocyanin-alginate composite prepared at a phycocyanin/alginate ratio of 40/60 for 20 h at 20 °C gave the best properties in terms of flexibility of film and releasing properties of phycocyanin.
  8. Suhaimi SH, Hasham R, Hafiz Idris MK, Ismail HF, Mohd Ariffin NH, Abdul Majid FA
    Molecules, 2019 Nov 18;24(22).
    PMID: 31752230 DOI: 10.3390/molecules24224183
    Primarily, optimization of ultrasonic-assisted extraction (UAE) conditions of Orthospihon stamineus was evaluated and verified using a central composite design (CCD) based on three factors including extraction time (minutes), ultrasound amplitude (A), and solvent concentration (%). The response surface methodology (RSM) was performed to develop an extraction method with maximum yield and high rosmarinic acid content. The optimal UAE conditions were as follows: extraction time 21 min, ultrasound amplitudes 62 A, and solvent composition 70% ethanol in water. The crude extract was further fractionated using solid-phase extraction (SPE), where six sequential fractions that varied in polarity (0-100% Acetonitrile in water) were obtained. Next, the six fractions were evaluated for their antioxidant and anti-cancer properties. This study found that Fraction 2 (F2) contained the highest rosmarinic acid content and showed the strongest antioxidant activity. Additionally, F2 showed an anti-proliferative effect against prostate cancer (DU145) with no harmful effect on normal cells.
  9. Noor NM, Khan AA, Hasham R, Talib A, Sarmidi MR, Aziz R, et al.
    IET Nanobiotechnol, 2016 Aug;10(4):195-9.
    PMID: 27463789 DOI: 10.1049/iet-nbt.2015.0041
    Virgin coconut oil (VCO) is the finest grade of coconut oil, rich in phenolic content, antioxidant activity and contains medium chain triglycerides (MCTs). In this work formulation, characterisation and penetration of VCO-solid lipid particles (VCO-SLP) have been studied. VCO-SLP were prepared using ultrasonication of molten stearic acid and VCO in an aqueous solution. The electron microscopy imaging revealed that VCO-SLP were solid and spherical in shape. Ultrasonication was performed at several power intensities which resulted in particle sizes of VCO-SLP ranged from 0.608 ± 0.002 µm to 44.265 ± 1.870 µm. The particle size was directly proportional to the applied power intensity of ultrasonication. The zeta potential values of the particles were from -43.2 ± 0.28 mV to -47.5 ± 0.42 mV showing good stability. The cumulative permeation for the smallest sized VCO-SLP (0.608 µm) was 3.83 ± 0.01 µg/cm(2) whereas for larger carriers it was reduced (3.59 ± 0.02 µg/cm(2)). It is concluded that SLP have the potential to be exploited as a micro/nano scale cosmeceutical carrying vehicle for improved dermal delivery of VCO.
  10. Subarmaniam T, Mahmad Rusli RN, Perumal KV, Yong YK, Hadizah S, Othman F, et al.
    Int J Mol Sci, 2023 Mar 09;24(6).
    PMID: 36982300 DOI: 10.3390/ijms24065224
    Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.
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