Biosynthesis pathway of heme in mitochondria of animal cell.

Biosynthesis pathway of heme in mitochondria of animal cell.

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5-Aminolevulinic acid (5-ALA) is a delta amino acid naturally present in every living cell of the human body. 5-ALA is produced in the mitochondria as the first product of the porphyrin synthesis pathway and composes heme; exogenously supplemented 5-ALA helps in upregulating mitochondrial functions. Mitochondrial dysfunction has been associated wit...

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... Antidiabetic medications are employed to stimulate potassium channels through an adenosine triphosphate (ATP)-dependent pathway in the treatment of diabetes (Table S1). However, no bioassay have been developed to date to assess antidiabetic pharmaceuticals using this particular MoA (Rehani et al., 2019). Parrella et al. (2014) assessed the biological activity of cytotoxic drugs such as doxorubicin in water systems by MTT ((3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) cell proliferation assay that contribute to evaluate the cytostatic environmental risk. ...
... Dietary supplements are generally considered safe when used as directed. However, there can be concerns about product quality, purity, and potential interactions with other medications or health conditions (Rehani et al., 2019). ...
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The prevalence of diabetes has surged worldwide, necessitating innovative approaches to complement conventional therapies. Dietary supplements derived from natural sources have gained attention for their potential roles in diabetes management. This review delves into the pharmacognosy and pharmacological aspects of select dietary supplements commonly employed in diabetes care, including cinnamon, fenugreek, bitter melon, Gymnema sylvestre, and berberine. The review synthesizes clinical evidence supporting their efficacy in glycemic control, elucidates safety considerations, and navigates regulatory challenges. While clinical studies exhibit promising outcomes, variability in individual responses and product quality underscores the importance of personalized approaches and robust quality control measures. The review also explores future research directions, such as personalized therapies, enhanced standardization methods, and novel delivery systems. In conclusion, dietary supplements offer potential as adjuncts to diabetes management, but a comprehensive understanding of their pharmacological properties, safety profiles, and regulatory context is essential for optimizing their role in diabetes care.
... Nowadays, numerous scientists pay their efforts towards anti-DM drug development due to the lack of a single successful drug for achieving the goal of blood glucose control. The recommendation for diabetes treatment is to combine drugs with different modes of action for controlling blood glucose effectively [8,9]. Hence, the preference is shifting towards exploring new lead compounds from herbal medicine, which may offer various modes of action and effective results with less side effects [10,11]. ...
... Briefly, each sample at various concentrations in 50 μL of 0.57 U/mL α-glucosidase enzyme was equally pre-mixed with 50 mM phosphate buffer, pH 6.9 for 10 min at 37 • C. Subsequently, 50 μL of a 5 mM pNPG substrate was added to the reaction mixture and incubated for 30 min. The reaction was stopped by 50 μL of a 1 M sodium carbonate solution (Na 2 CO 3 ), and the absorbance at 405 nm was immediately measured using a microplate reader (DTX880 (7), and pinocembrin (8) were found within the leaf crude extract. 3-Farnesyl indole (9), onysilin (10), cinchonain la (11), and cinchonain lb (12) were identified from the twig of U. dulcis. ...
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Medicinal plants have long been a source of lead compounds for drug discovery. Among these, the Annonaceae family has gained recognition for its potential to yield novel compounds, particularly those that can be used in the development of drugs targeting chronic diseases like diabetes mellitus (DM). We employed various chromatographic methods to isolate bioactive compounds from the roots, leaves, and twigs of Uvaria dulcis Dunal. We used spectroscopic methods to determine the chemical structures of these compounds. We successfully identified twelve known compounds from various parts of U. dulcis: patchoulenon, polygochalcone, 2′3′-dihydroxy-4′,6′-dimethoxydihydrochalcone, 2′,3′-dihydroxy-4′,6′-dimethoxychalcone, chrysin, techochrysin, 8-hydroxy-5,7-dimethoxyflavanone, pinocembrin, 3-farnesylindole, onysilin, cinchonain la, and cinchonain lb. Interestingly, cinchonain la and cinchonain lb exhibited more potent anti-α-glucosidase activity than acarbose (standard drug), with IC50 values of 11.88 ± 1.41 μg/mL and 15.18 ± 1.19 μg/mL, respectively. Cinchonain la inhibited the DPP-IV enzyme, with IC50 value lower than the standard compound (diprotin A) at 81.78 ± 1.42 μg/mL. While 2′,3′-dihydroxy-4′,6′-dimethoxychalcone show more potent inhibitory effect than standard drug with IC50 value of 8.62 ± 1.19 μg/mL. Additionally, at a concentration of 10 μg/mL, cinchonain lb and 2′,3′-dihydroxy-4′,6′-dimethoxychalcone promoted glucose uptake in L6 myotubes cells to the same extent as 100 nM insulin. These findings suggest that cinchonain la, cinchonain lb, and 2′,3′-dihydroxy-4′,6′-dimethoxychalcone are the U. dulcis-derived bioactive compounds that hold promise as potential structures to use in the development of anti-diabetic drugs.
... Endocrines 2024, 5, FOR PEER REVIEW 14 Figure 2. Foods, especially refined carbohydrates, have the greatest effect on blood glucose. This figure is adapted from [58] and summarizes the primary actions of common diabetes medications; however, not all known actions are depicted. Medications target specific actions to manage blood glucose; however, regardless of the medication used, the wrong foods will raise blood glucose. ...
... When using urine color and color charts, one consideration is that vitamins B2 and B12 in excess will cause a bright yellow color, and some medications will affect urine color (see MedlinePlus [72]). [58] and summarizes the primary actions of common diabetes medications; however, not all known actions are depicted. Medications target specific actions to manage blood glucose; however, regardless of the medication used, the wrong foods will raise blood glucose. ...
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Medical (healthcare) deserts and food deserts, either separate or combined, exist in rural areas, globally. The physicians and other healthcare professionals who serve rural and other underserved populations, to some extent, also experience life in these areas. Dietary guidelines, from expert societies, for people with diabetes, have been helpful in guiding healthcare professionals through nutritional interventions. However, these guidelines are not designed for rural areas where healthcare resources are scarce, and access to the built environment for a healthy lifestyle and affordable healthy foods are not available. Therefore, the guidelines were reviewed, with rural physicians and healthcare professionals who work in underserved areas in mind, to assess their appropriateness. Based on the guidelines and other literature, potential solutions to guideline gaps are proposed to aid in providing nutritional therapy for the underserved. The overall goals are to improve the nutritional component of healthcare for underserved people with diabetes, and to begin the conversation around creating specific guidelines for rural physicians and other healthcare professionals, where patients are at a higher risk for diabetes.
... Tại Việt Nam, kết quả điều tra của Bộ Y tế năm 2021 cho thấy tỷ lệ mắc đái tháo đường ở người trưởng thành ước tính là 7,1%, tương đương với khoảng gần 5 triệu người đang mắc bệnh đái tháo đường [2]. Trong phát đồ hiện nay, sử dụng chủ yếu các thuốc có nguồn gốc hóa dược để điều trị, việc sử dụng các thuốc này dù mang lại hiệu quả lâm sàng nhưng cũng tiềm ẩn nguy cơ xảy ra các tác dụng phụ [3]. Do đó, xu hướng hiện nay của thế giới và Việt Nam là nghiên cứu bào chế các sản phẩm có nguồn gốc dược liệu để hỗ trợ và điều trị bệnh đái tháo đường vừa cho hiệu quả vừa hạn chế các tác dụng phụ cho người sử dụng. ...
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Đặt vấn đề: Lá Xoài chứa thành phần chính mangiferin đã được nhiều tài liệu chứng minh có công dụng hạ đường huyết, tuy nhiên các nghiên cứu tại Việt Nam về độc tính cũng như tác dụng hạ đường huyết của lá Xoài còn hạn chế. Mục tiêu nghiên cứu: Đánh giá độc tính cấp và tác dụng hạ đường huyết của cao chiết lá Xoài trên mô hình chuột nhắt trắng. Đối tượng và phương pháp nghiên cứu: Cao chiết lá Xoài được tinh chế hóa với hàm lượng mangiferin đạt 90%. Thử nghiệm độc tính cấp của cao chiết lá Xoài được tiến hành trên chuột Swiss albino dựa theo tài liệu “Phương pháp xác định độc tính của thuốc” của tác giả Đỗ Trung Đàm; Tác dụng hạ đường huyết của cao chiết lá Xoài được đánh giá bằng phương pháp gây tăng đường huyết chuột nhắt bằng hóa chất Alloxan, chuột tăng đường huyết sau đó được phân thành các lô như sau: lô chứng âm-không điều trị, lô chứng dương-điều trị bằng Metformin 500 mg/kg/ngày và 2 lô thử nghiệm lần lượt cho uống cao chiết lá Xoài với mức liều 100 và 200 mg/kg/ngày trong 21 ngày. Kết quả đường huyết được ghi nhận sau mỗi tuần, đối chiếu giữa 2 lô thử nghiệm với lô chứng âm, lô chứng dương và lô sinh lý. Kết quả: Tất cả chuột trong các lô đều còn sống và không có biểu hiện độc tính trong thời gian thử nghiệm dù đã dùng liều tối đa 5.000 mg/kg trọng lượng. Mức đường huyết của lô thử nghiệm giảm đáng kể (p<0,05) so với lô chứng âm và tương đương lô chứng dương. Kết luận: Chưa phát hiện độc tính cấp của cao chiết lá Xoài khi đã thử nghiệm đến mức liều 5.000 mg/kg và có tác dụng hạ đường huyết có ý nghĩa thống kê với mức liều 100 và 200 mg/kg trọng lượng.
... The current form of management is mainly by administration of oral hypoglycaemic agents (OHAs) as single or in combination with insulin to control the blood glucose level. These agents act by improving insulin release, decrease glucose production and enhance the peripheral glucose uptake and will target on insulin signalling pathways to reverse the progression of T2DM (Rehani et al. 2019). The issue with existing OHA or insulin is the side effects, particularly hypoglycaemia which lead to the discomfort or even health hazards to the patients. ...
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The emergence of nanotechnology has become more popular, and the progress had sparked much development in nanoparticle synthesis, including selenium. Studies associated with the therapeutic abilities and physicochemical properties of selenium nanoparticles (SeNPs) are rapidly growing and gaining interest from many researchers. This review discusses on the fundamental components of selenium, different approaches in synthesizing selenium nanoparticles, its remedial properties and potential in biomedical application. Herein, primary focus will be given to the action of selenium nanoparticles mechanism in improving diabetes mellitus symptoms and complications in animal studies. It is known that selenium is an important micronutrient found in humans, plants and animals that can be incorporated as selenoprotein in the human body. Analysis and comparison on the findings enlighten that SeNPs demonstrated ameliorative effect on diabetes complications due to their antidiabetic, antioxidant, anti-inflammatory and lipid-lowering characteristics.
... Type 2 DM is caused by a progressive imbalance between diet and physical activity (obesity), leading to insulin resistance, with a decrease in production level underlying the disease [96]. Insulin is the main regulating hormone in the development of type 2 DM in which it regulates blood sugar levels in the body by allowing glucose to enter the body's cells [97]. ...
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Amphibians have been consumed as an alternative protein source all around the world due to their delicacy. The skin of edible amphibians, particularly frogs and giant salamanders, always goes to waste without further utilization. However, these wastes can be utilized to extract protein and bioactive peptides (BPs). Various BPs have been extracted and reported for numerous biological activities such as antioxidant, antimicrobial, anticancer, antidiabetic, etc. The main BPs identified were brevinins, bombesins, dermaseptins, esculentins, magainin, temporins, tigerinins, and salamandrins. This review provides a comprehensive discussion on various BPs isolated and identified from different amphibian skins or skin secretion and their biological activities. The general nutritional composition and production statues of amphibians were described. Additionally, multiple constraints against the utilization of amphibian skin and secretions are reported. Finally, the prospective applications of BPs in food and biomedical industries are presented such as multifunctional food additives and/or supplements as well as drug delivery agents.
... A natural amino acid, 5-aminolevulinic acid (5-ALA) commonly occurs in animals, plants, fungi and bacteria. So far, 5-ALA has been clinically used for metabolic improvement in human diseases, including diabetes [24] and the diagnosis and treatment of various cancers [25]. The conjugation of eight molecules of 5-ALA produces protoporphyrin IX (PPIX), which produces heme by the insertion of a ferrous ion [26]. ...
... Infected cell supernatants were then harvested and quantified by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). As 'SFC only' did not show antiviral activity in the previous report [24], the efficacy of 'SFC only' was not examined in the present study. ...
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Background Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to emerge in 2020 and have been spreading globally during the coronavirus disease 2019 (COVID-19) pandemic. Despite the presence of different COVID-19 vaccines, the discovery of effective antiviral therapeutics for the treatment of patients infected with SARS-CoV-2 are still urgently needed. A natural amino acid, 5-aminolevulinic acid (5-ALA), has exhibited both antiviral and anti-inflammatory activities. In a previous study, we demonstrated an in vitro antiviral effect of 5-ALA against SARS-CoV-2 infection without significant cytotoxicity. In the present study, we sought to investigate whether 5-ALA with or without sodium ferrous citrate (SFC) can inhibit in vitro both the original SARS-CoV-2 Wuhan strain and its variants, including the Alpha, Beta, Gamma and Delta strains. Methods The antiviral activity of ALA with or without SFC was determined in Vero-E6 cell. The virus inhibition was quantified by real time RT-PCR. Results Co-administration of 5-ALA and SFC inhibited the Wuhan, Alpha and Delta variants of SARS-CoV-2 with IC 50 values of 235, 173 and 397 µM, respectively, and the Beta and Gamma variants with IC 50 values of 1311 and 1516 µM. Conclusion Our study suggests that 5-ALA with SFC warrants accelerated clinical evaluation as an antiviral drug candidate for treating patients infected with SARS-CoV-2 variants.
... Recently, many anti-diabetic drugs have been developed and consist of multiple modes of action to control blood sugar levels, such as inhibiting metabolic enzymes (such as α-amylase and α-glucosidase), blocking the dipeptidyl peptidase-IV (DPP-IV) enzyme, and enhancing glucose uptake [8,9]. However, there is no successful remedy for curing T2DM. ...
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Bioactive compounds from medicinal plants are good alternative treatments for T2DM. They are also sources of lead molecules that could lead to new drug discoveries. In this study, Bauhinia strychnifolia Craib. stem, a traditional Thai medicinal plant for detoxification, was extracted into five fractions, including crude extract, BsH, BsD, BsE, and BsW, by ethanolic maceration and sequential partition with hexane, dichloromethane, ethyl acetate, and water, respectively. Among these fractions, BsE contained the highest amounts of phenolics (620.67 mg GAE/g extract) and flavonoids (131.35 mg QE/g extract). BsE exhibited the maximum inhibitory activity against α-glucosidase (IC50 1.51 ± 0.01 µg/mL) and DPP-IV (IC50 2.62 ± 0.03 µg/mL), as well as dominantly promoting glucose uptake on 3T3-L1 adipocytes. Furthermore, the four compounds isolated from the BsE fraction, namely resveratrol, epicatechin, quercetin, and gallic acid, were identified. Quercetin demonstrated the highest inhibitory capacity against α-glucosidase (IC50 6.26 ± 0.36 µM) and DPP-IV (IC50 8.25 µM). In addition, quercetin prominently enhanced the glucose uptake stimulation effect on 3T3-L1 adipocytes. Altogether, we concluded that quercetin was probably the principal bioactive compound of the B. strychnifolia stem for anti-diabetic, and the flavonoid-rich fraction may be sufficiently potent to be an alternative treatment for blood sugar control.
... In plants, magnesium is incorporated into chlorophyll, and 5-ALA is the source of chloroplasts that are essential for plant photosynthesis. Given this beneficial heme-forming ability, 5-ALA has been widely used for treating several human diseases and for metabolic improvement, such as hyperglycemia and sleep disorder in the form of a bioactive compound [1][2]. ...
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Introduction: The aim of this study was to examine the effects of a bioactive compound, 5-aminolevulinic acid (5-ALA), which has been reported to exhibit an immune-boosting effect, using a classical live swine fever (CSF) vaccine experimental model in pigs. Methods: First, the effect of two different 5-ALA doses was evaluated by measuring the blood CSF viral load in male and female micro miniature pigs after vaccination with live vaccines. The CSF vaccine had a low inducing effect on antibody production in females, which improved after administration of 5-ALA by enhancing Th2 immunity as indicated by elevated interleukin-10 levels. Next, using male micro miniature pigs, the change in body weight was measured from the time before inoculation with the live vaccine to 28 days after inoculation, and the pattern of IgM and IgG antibody production after 5-ALA administration was examined. Results: Preventive doses of 5-ALA enabled the continuous production of IgG antibodies at the same rate as found in control pigs not receiving 5-ALA; however, the switch to IgG production was delayed during 5-ALA treatment. Oral administration of 5-ALA kept the testing male pigs healthy, showing normal growth. Conclusions: This suggested that the heme synthesis-promoting effects of 5-ALA simultaneously promoted the conversion of B cells into plasma cells.Keywords: functional food, 5-ALA, human equivalent dose, pig, classical swine fever