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Antioxidative and anti-proliferative potential of Curculigo orchioides Gaertn in oxidative stress induced cytotoxicity: In vitro, ex vivo and in silico studies
... 10). Also, piperine interaction with superoxide dismutase has been reported with -4.2 kcal/mol binding energy [58] . The binding energy of glutathione-s-transferase with EGCG, withaferin A, EGCG+withaferin A and reference was -6.1, -6.9, -9.2 and -5.5 kcal/mol respectively ( fig. ...
... 10). Capsicin interaction with glutathione-s-transferase has been previously reported to exhibit a -7.9 kcal/mol binding energy [58] , which is greater than the energy obtained for individual ligands, but less than the energy obtained upon MLSD analysis in the current study. The binding energy of glutathione peroxidase with (1), (2), (3) and reference was -6.7, -8.3, -8.8 and -5.4 kcal/mol respectively. ...
... The binding energy of glutathione peroxidase with (1), (2), (3) and reference was -6.7, -8.3, -8.8 and -5.4 kcal/mol respectively. The binding energy of glutathione peroxidase with piperine has been reported as -6.2 kcal/mol [58] . Further, the binding energy of catalase with (1), (2), (3) and reference was -7.3, -8.0, -8.3 and -6.4 kcal/mol respectively. ...
Phytoconstituents epigallocatechin gallate and withaferin A, found in Camellia sinensis (Kangra green tea) and Withania sominifera (Ashwagandha) respectively, were explored for their binding affinity towards various enzymes involved in the skin-aging process. Epigallocatechin gallate and withaferin A were analyzed for their physiochemical properties, drug-likeness and human intestinal absorptivity using Data Warrior, Molsoft and SwissADME (boiled egg model) respectively. Molecular docking analysis for different enzymes involved in aging (collagenase, elastase and hyaluronidase), antioxidant enzymes (superoxide dismutase, glutathione-s-transferase, glutathione peroxidase and catalase) and mitochondrial enzymes (nicotinamide adenine dinucleotide (NAD)+hydrogen (H) dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and adenosine triphosphate synthase) was carried out for epigallocatechin gallate alone (1), withaferin A alone (2), epigallocatechin gallate and withaferin A in combination (3) and a reference molecule. Autodock Vina was employed to carry out individual molecular docking as well as multiple ligand simultaneous docking. The results were analyzed in terms of binding energy and different interacting residues. Interestingly, (3) displayed a higher binding affinity towards all the aging and antioxidant enzymes as compared to (1), (2) and the references. Moreover, the combination of the constituents exhibited better binding for most of the mitochondrial enzymes. Additionally, molecular dynamics simulations were performed to estimate stability and flexibility of best complexes, while collagenase activity colorimetric assay was carried out to study the effects of (1), (2) and (3) on collagenase. The in vitro analysis indicated a 1.5 times increase in collagenase inhibition upon using (3) as compared to ascorbic acid (standard). Overall, the results indicate that epigallocatechin gallate and withaferin A, in combination, may potentially inhibit skin-aging, while enhancing antioxidant effects of various enzymes, and warrant further experimental validation.
... Epidemiological studies have identified a positive correlation between the increased consumption of natural products which contained various phytoconstituents with a decreased risk of cancer [1]. Naringenin (flavanone) and quercetin (flavonol), two representative phytoconstituents widely used in the human diet, have been shown to be positively associated with beneficial health effects [2]. ...
... Four common apoptosis-regulated genes, including p21, p53, Bcl-2 and Bax, were further assessed using RT-qPCR. Bcl-2 is extensively considered a therapeutic target for apoptosis-inducing anticancer approaches as it is often overexpressed in many cancers [1,34]. In contrast, p21, p53 and Bax are considered the apoptosis-induced genes [35]. ...
... Taken together, cell growth arrest Four common apoptosis-regulated genes, including p21, p53, Bcl-2 and Bax, were further assessed using RT-qPCR. Bcl-2 is extensively considered a therapeutic target for apoptosis-inducing anticancer approaches as it is often overexpressed in many cancers [1,34]. In contrast, p21, p53 and Bax are considered the apoptosis-induced genes [35]. ...
Tamoxifen is commonly used to treat estrogen receptor-positive breast cancer and hepatocellular carcinoma. Phytoconstituents are considered candidates for chemopreventive drugs in cancer treatment. However, it remains unknown what would happen if tamoxifen and phytoconstituents were administrated simultaneously. We aimed to observe the synergistic antitumor effects of tamoxifen and naringenin/quercetin on human hepatic carcinoma and to explore the potential underlying molecular mechanisms. The HepG2 cell line was used as an in vitro model. Cell proliferation, invasion, migration, cycle progression and apoptosis were investigated along with reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) repression. The signaling pathways involved were identified using real-time quantitative polymerase chain reaction analysis. As the results show, tamoxifen in combination with higher concentrations of naringenin or quercetin significantly inhibited cell growth compared to either agent alone. These antiproliferative effects were accompanied by the inhibition of cell migration and invasion but the stimulation of cell apoptosis and loss of ΔΨm, which depended on the ROS-regulated p53 signaling cascades. Conversely, lower concentrations of naringenin and quercetin inhibited the tamoxifen-induced cell antiproliferative effects by regulating cell migration, invasion, cycle and apoptosis. Taken together, our findings revealed that phytoconstituents exerted contradictory cytoprotective and cytotoxic effects induced by tamoxifen in human hepatic cancer.
... Rimpang tumbuhan ini secara tradisional digunakan sebagai antiosteoporosis, antioksidan, estrogenik, neuroprotektif, antibakteri, antiasma, antibronkhitis, antiapoptosis, antikanker, dan juga sebagai diuretik dan afrodisiak (Hejazi et al. 2018). Kandungan kimianya berupa glukosida orcinol memiliki aktivitas antioksidan (Wu et al. 2005), glikosida sikloartan digunakan sebagai obat leukemia (Yokosuka et al. 2010), curculigoside F dapat menghambat virus hepatitis B (HBV) e antigen (HBeAg) pada pengujian dengan galur sel HepG2.2.15 (Zuo et al. 2010) , golongan glikosida klorofenol seperti curculigine M, curculigine N, dan curculigine O mendorong proliferasi osteoblas . ...
... Metabolit sekunder yang banyak dimanfaatkan sebagai antioksidan dan antidiabetes yang dipicu oleh radikal bebas adalah golongan polifenol (Ghasemzadeh dan Ghasemzadeh 2011;Hejazi et al. 2018). Derivat metabolit sekunder sangat bervariasi, sehingga perlu adanya suatu metode untuk menentukan gugus fungsi yang berperan sebagai antioksidan pada spesies radikal bebas. ...
... Metabolit sekunder tumbuhan terutama golongan fenol dan flavonoid banyak dieksplorasi sebagai antioksidan alami, baik secara in vitro maupun in vivo, serta in silico (Hejazi et al. 2018). Senyawa ini, memiliki kemampuan transfer atom hidrogen (HAT) dan transfer elektron (ET) (Apak et al. 2007). ...
Diabetes mellitus (DM) is a disease caused by lacking of insulin production or by the inability of cells to respond to insulin (insulin resistance). According to the International Diabetes Federation, diabetes cases in the world reach 425 millions and are predicted to increase to 625 millions by 2045. The trend of increasing cases and death rates due to diabetes needs a special attention, especially in the pattern of it’s treatment. Diabetes treatment using natural ingredients is one of the most researched fields in the world because it is effective and safe. Curculigo latifolia Dryand. ex W.T. Aiton and Curculigo orchioides Gaertn. belonging to the family Hypoxidaceae, annual herbs with lanceolate-shaped leaves or parallel lanceolate arranged in a rosette, with yellow flowers, very short stems, and have a long cylindrical rhizome. A total of 39 species of this genus are accepted in the World Checklist of Selected Plant Families (WCSP 2020), including these two species. Both species are known as traditional medicinal plants in various tropical regions. Rhizome of Curculigo spp. is one of the raw material sources for traditional medicine to treat DM; this pharmacological effect comes from secondary metabolites. Those compounds are distributed and accumulated in certain secretory structures within the plant. However, the activities of the active compounds in such diverse plant organs are very difficult to be determined in a short time, as well as its pharmacokinetic and pharmacodynamics parameters. In addition, compounds produced under normal conditions in the nature are very low. Therefore, this study aimed to determine the distribution of secretory structures and the producing and/or accumulating sites of the bioactive compounds through histochemical tests, to determine which bioactive compounds contribute the most to diabetes mellitus, especially in antioxidant activity and α-glucosidase inhibition, and to determine their pharmacokinetics and pharmacodynamics parameters. In addition, this research was also carried out to produce callus and micropropagate the plants, as well as to ensure the existence of those bioactive compounds in in vitro cultured callus. Determination of secretory structure using cross sections of fresh samples according to plant anatomical procedures and histochemical analysis using several reagents were performed to detect groups of metabolites. Determination of bioactive compounds was done using an analysis combination on biological activities (antioxidants and α-glucosidase inhibition) with metabolite fingerprint using FTIR and metabolite profiling with UHPLC-Q-Orbitrap HRMS-based metabolomic and chemometric techniques using partial least squares regression analysis (PLSR). Pharmacokinetics and pharmacodynamics parameters were determined using Lipinski's rule of five, pharmacological networks using Cytoscape, and molecular docking with PyRx, PyMOL, and BIOVIA Discovery Studio. Callus production and micropropagation began with explant sterilization using environmental-friendly sterilants. Callus initiation and organogenesis were induced by various concentrations of auxins and cytokinin. Metabolomic analysis based on metabolite profiling using UHPLC-Q-Orbitrap HRMS and chemometric techniques using principal component analysis (PCA) were carried out to identify the compounds in the callus and plantlet’s leaves. The anatomical and histochemical analysis of fresh tissues showed that all organs contained secretory structures that accumulated various metabolites. The secretory structures identified in the roots, rhizomes, petiole, and leaves of these two species were secretory cavities and idioblasts. The group of compounds identified were phenols, alkaloids, terpenes, essential oils, and lipophilic. They were also spread over some common tissues of the organs. Based on metabolomic and chemometric analysis the main compounds contributing in antioxidant and α-glucosidase inhibition activities were notified from the phenol group, such as curculigoside B, orchioside B; 2,4-Dichloro-5-methoxy-3-methylphenol, orcinol glucoside; 1,1-Bis-(3,4-dihydroxyphenyl)-1-(2-furan)-methane; from the terpene group, such as: curculigosaponin G, H, and I; from the norlignan group, (1S,2R)-O-Methylnyacoside; and from the aldehyde group, 5-hydroxymethylfural, while the functional groups included O–H, C=O, C–O, C–H. These compounds were accumulated more abundantly in the leaves of C. latifolia (DLSP) from Sinjai-Palangka and C. orchioides (DOGM) from Gowa-Malakaji. Pharmacokinetic parameters showed that 33 out of the 79 compounds were able to be absorbed properly, while some compounds did not meet the requirements. The latter compounds must be converted into aglycones if they will be used as medicinal substances. The cynanuriculoside ligand A_qt based on pharmacological network analysis and molecular docking was able to interact pharmacodynamically with hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) target via 6NJ7 receptor, resulting an affinity of –12.0 (kcal mol–1), with amino acid residues in the form of Ala 226, Leu 126, Val 180, Tyr 183, Leu 215, Ser 170, Ile 121, and Val 168. The sterilization of explants with the lowest concentrations of sterilizing agents and a short contact time with the explants produced 90% sterile cultures. The best combination of plant growth regulators (PGRs) for callus induction in C. latifolia and C. orchioides were BAP : IBA at 3 : 5 and 5 : 3 mg L–1, respectively. The callus were green and white, with a compact consistency. Those combinations of PGRs also regenerated shoots and roots in both species. The secretory structures found in the callus were secretory cavities and idioblast cells. In the callus of C. latifolia, phenol was identified in the organogenic parts and epithelium cells of the secretory cavities, and the essential oils were in idioblast cells; while C. orchioides’ callus contained phenol in the organogenic parts only. The compounds that had contribution in antioxidant and α-glucosidase inhibition activities, such as 1,1-Bis-(3,4-dihydroxyphenyl)-1-(2-furan)-methane, (1S,2R)-O-Methylnyacoside; 2,4-Dichloro-5-methoxy-3-methylphenol, curculigoside B, curculigosaponin G, H, and I; orchioside B, and orcinol glucoside were also identified in the callus and plantlet’s leaves. Most of them belong to the phenol group. The general conclusion of this study is that histochemical techniques revealed that there were differences in the accumulation sites of compounds among organs of Curculigo spp. Histochemically, phenolic compounds were identified in the rhizome, petiole, and leaves of C. latifolia, while in C. orchioides they were only identified in the rhizome. Phenolics were also found in the organogenic callus of these two species. From the metabolomic-chemometric analysis, compounds that contributed greatly to the antioxidant and α-glucosidase inhibition activities were accumulated in the leaves of both species. From the pharmacological network and molecular docking approaches, cynanuriculoside A_qt, curculigosaponin L_qt, and curculigenin B were confirmed to have potential for the treatment of diabetes mellitus. The compounds found in the plant’s organs of C. latifolia and C. orchioides that contribute greatly in antioxidant and α-glucosidase inhibition activities were also identified in the callus and plantlet’s leaves resulted from in vitro cultures. Some of which even demonstrated higher concentration (peak area) than those of the original plant organs.
... Cancer remains a significant global public health problem in diverse countries (Duan et al., 2018). The development of cancer is associated with longevity, environmental factors, and lifestyles (Adhami et al., 2009), risk factors may cause aberrations in the cell signaling essentials for the typical development of the biological processes, thus causing cancer (Hejazi et al., 2018). Specifically, cervical cancer is the third or fourth most frequently diagnosed cancer in younger women and is the principal cause of cancer death (Abou-Hashem et al., 2019, Yang et al., 2018. ...
... ACK-1 is over-expressed in different types of cancers, including ovarian cancer (Zhao et al., 2018). Bcl-2 controls the mitochondrial suicide program apoptosis negatively (Edlich 2018;Timucin et al., 2019;Hejazi et al., 2018) reported the downregulation of Bcl-2 in HepG2, Hela and MCF-7 cells treated with different fractions of Curculigo orchioides (Hejazi et al., 2018). Frat is a regulator of Wnt/-catenin; however, the Frat-1 overexpression is associated with different human cancers (van der Wal T, 2020). ...
... ACK-1 is over-expressed in different types of cancers, including ovarian cancer (Zhao et al., 2018). Bcl-2 controls the mitochondrial suicide program apoptosis negatively (Edlich 2018;Timucin et al., 2019;Hejazi et al., 2018) reported the downregulation of Bcl-2 in HepG2, Hela and MCF-7 cells treated with different fractions of Curculigo orchioides (Hejazi et al., 2018). Frat is a regulator of Wnt/-catenin; however, the Frat-1 overexpression is associated with different human cancers (van der Wal T, 2020). ...
Polyphenols may be an effective therapy for both the prevention and treatment of cancer. Previous studies have found that these compounds may inactive Hela cells, which may even be converted into a normal cells post-treatment. The present study extracted phenolic compounds from pomegranate peel, with the polyphenols then purified using different solvents and identified by means of high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS). Once the phenolic compounds had been purified, we evaluated their cytotoxic effects on both the Hela and NIH-3T3 cell lines, on which an apoptosis assay was also carried out. Additionally, apoptosis assay was carried out on Hela and NIH-3T3. Lastly, the proteome profile was analysed via two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). We isolated and then purified punicalagin and ellagic acid (EA) from pomegranate peel, with both compounds likely to have a cytotoxic effect on Hela and NIH-3T3. However, this effect depends on both concentration and exposure time. Results obtained using a Cayman commercial assay kit suggests that punicalin and EA regulate the apoptosis on the Hela and NIH-3T3 cell lines. Finally, we observed that polyphenols compounds regulate the expression of proteins related to apoptosis. In conclusion, punicalin and EA have a cytotoxic effect on Hela and, furthermore, reactive the apoptotic pathway in this cell.
... In the Philippines, the rhizomes are used as a tonic, pectoral, diuretic, and aphrodisiac alone or in conjunction with carminative medications, and are put into a salve for itchy skin and other skin diseases Burkill (1966). A study indicates that Curculigo orchioides Gaertn fractions and compounds efficiently suppressed H2O2 induced oxidative stress by boosting antioxidant enzyme content and have cytotoxic potential on cancer cell lines HepG2, HeLa, and MCF-7 Hejazi et al. (2018). The various medicinal properties of Curculigo orchioideshas been listed in the Table 3. ...
... Furthermore, additional research may be conducted on the pathways involved at the cellular level, which can provide a concise overview of the active cell machinery engaged in programmed cell death. Understanding the molecular mechanisms that drive apoptosis in response to anticancer medicines, as well as how cancer cells avoid apoptotic death, opens up new avenues for a more balanced approach to developing molecular-targeted cancer treatments Hejazi et al. (2018). Curculigo orchioides was also shown to lower hearing threshold shifts, central auditory function damage, and cochlear function deficits, indicating that it might be used as a possible therapeutic natural product for noise-induced hearing loss in mice Hong, You, and Kang (2011). ...
Medicinal plants have been utilized to heal a variety of ailments throughout human civilization. Over-exploitation of these therapeutic plants has resulted in their extinction. Curculigo orchioides Gaertn. (Hypoxidaceae) often known as black muesli in India, is an endemic herbaceous plant that must be protected. The plant's rhizome and tuberous roots have been widely employed in traditional systems of medicine in India, for the treatment of numerous ailments such as jaundice, asthma, and diarthrosis. The rhizome juice has also been used as a tonic to treat impotency, prevent bone loss, and for anti-diabetic, anti-tumour, and antibacterial activities. The article presents a review on basic biology, in-vitro propagation techniques, medicinal properties, petrochemical constituents and toxicology of this important plant.
... The accumulation of secondary metabolites was reported to have an essential role in plant tolerance to biotic and abiotic stresses. The plants adapt to fluctuating environmental conditions, among others, due to their high phenolic content and their antioxidant capacity (Hashim et al., 2020). Callus and plantlet leave also accumulated a relatively high level of phenols. ...
... Additionally, they noticed that callus generated from rhizomal explant and rhizome collected from the field performed superior antioxidant activities than those from leaf-derived callus and the original leaves. A similar result was also obtained by Hejazi et al. (2018) and Kushalan et al. (2022), who reported that the rhizome of Curculigo orchioides had the highest activity as an antioxidant. Based on the collected information and our results, it is suggested that the rhizome of Curculigo spp. is the main site of secondary metabolites accumulation, at least those exerting as antioxidants. ...
Curculigo latifolia is traditionally used in herbal medication. We determined the total phenolics profile, antioxidant capacity, and metabolomics of in vitro propagules compared to the mother plant organs, intending to disclose the prospective of in vitro cultured propagules as an alternative source of the essential metabolites of this species. Phenolic content was investigated by colorimetry. Antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing/antioxidant power (FRAP) assays. Ultrahigh-performance liquid chromatography-quadrupole-orbital ion trap analyzer-high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) and chemometrics were exploited for comparative analyses of the metabolite's composition. Total phenolic contents varied from 152.19 to 457.80 gallic acid equivalent g-1. The lowest DPPH and ABTS radical scavenging activities with the IC 50 values were obtained from the rhizome, and FRAP-reducing power activities were found in the leaves. UHPLC-Q-Orbitrap HRMS data and multivariate analysis classified and differentiated the compounds in the callus, plantlet leaves, rhizomes, petioles, and leaves. The marker compounds discriminating the in vitro propagules from the mother plant organs are orcinol glucoside, nyasicoside, and vanillin. This information would be valuable for the pharmaceutical industry, herbalists, or herbal medicine producers in using the plant organs as well as the in vitro callus.
... The present study showed that the CO contains a potent scavenger of DPPH free radical and has an EC50 value of 25.6±1.6 µg/mL (Table 03). Previous studies also showed a moderate DPPH radical scavenging capacity of C. curculigo 23 . The methanol extract of C. orchioides rhizomes was found to be moderately effective in scavenging DPPH radicals 30 . ...
... The methanol extract of C. orchioides rhizomes was found to be moderately effective in scavenging DPPH radicals 30 . The study of Hejazi et al., 2018 revealed that the DPPH radical scavenging capacity of aqueous extract of C. orchioides was EC 50 104.8±0.6 23 . Literature indicates that variation of plant secondary metabolites occur due to geographic location and connected environmental factors like temperature, rainfall, soil type, and composition 31 . ...
Curculigo orchioides Gaertn is a medicinal herb belonging to Amaryllidaceae family and is recognized as a potent source of biologically active compounds with many biological properties. The rhizome of the plant was used to prepare aqueous extracts in order to screen antioxidant and anti-inflammatory capacity. Total Phenolic Content (TPC) and Total Flavonoid Content (TFC) were evaluated to determine the phytochemical composition of the extracts. Antioxidant activity was screened using different assays, DPPH, total antioxidant activity, inhibition of protein oxidation, lipid peroxidation and deoxyribose oxidation and ferric ion reducing power. Anti-inflammatory activity was screened using human red blood cell membrane stability test and inhibition of protein denaturation assays. The TPC and TFC were 101.2±1.3 mg GA/g (Gallic Acid /g) and 178.4±2.4 mg EGCG/g (epigallocatechin gallate/g) respectively. The values of EC50 for DPPH, inhibition of deoxyribose oxidation, inhibition of lipid peroxidation, inhibition of protein oxidation and inhibition of BSA denaturation assays were 25.6±1.6, 10.1±1.0, 29.0±0.7, 82.6±3.9 and 32.9±3.5 µg/mL respectively. Further, RCO extract showed less ferric ion reducing ability. CO demonstrated comparable values for EC50 with Diclofenac sodium standard on membrane stabilizing activity (49.7±1.4 and 49.7±1.4 µg/mL respectively). Result of the study suggests that CO exerts antioxidant as well as anti-inflammatory activities by stabilizing biological membranes.
... Các hợp chất polysaccharid từ sâm cau thể hiện tác dụng chống ung thư rõ rệt trên khối u ác tính cổ tử cung ở chuột thử nghiệm, tăng cường đáng kể chức năng miễn dịch, tác động quá trình apoptosis biểu hiện bằng sự gia tăng chỉ số tuyến ức và lá lách. Hơn nữa, các polysaccharid điều chỉnh đáng kể sự biểu hiện của caspase-3, caspase-9 và protein (p53) đối với tế bào HeLa trong ống nghiệm [16,17,18]. ...
... Bằng phương pháp thử nghiệm hoạt tính gây độc và ức chế sự tăng sinh tế bào MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] trên dòng tế bào ung thư gan Hep-G2 (Hepatocellular carcinoma) kết quả Bảng 3.2 cho thấy: Mẫu SC, SC.E biểu hiện hoạt tính mạnh nhất đối với dòng tế bào ung thư Hep -G2 với giá trị IC 50 lần lượt là 37,2 μg/ml và 18,9 μg/ml các mẫu còn lại hoạt tính yếu hoặc không có hoạt tính kết quả này cũng tương đồng với những nghiên cứu đã được công bố [17][18][19]. chất có hoạt tính gây độc hoặc ức chế sự tăng sinh tế bào. Nguyên tắc của phương pháp là gián tiếp xác định hoạt tính của chất thử qua khả năng ức chế enzyme oxidoreductase phụ thuộc NAD(P)H của tế bào. ...
Cây sâm cau (Curculigo orchioides Gaertn) thuộc họ Hạ trâm (Hypoxidaceae) Curculigoosystemoides Gaertn. (Hypoxidaceae) là cây thân thảo sống lâu năm, thân rễ hình trụ dài. Thân rễ của loại cây này có nhiều dược tính cũng như các tính chất khác như: giải nhiệt, lợi tiểu, kích thích tình dục, bổ trĩ, trị trĩ, tiêu viêm, lở ngứa, chữa bệnh ngoài da, hen suyễn, viêm phế quản, vàng da, ung thư, làm lành vết thương do tiêu chảy …Thử hoạt tính chống oxi hóa bằng các phương pháp loại bỏ các gốc tự do tạo bởi 1,1-diphenyl-2-picrylhydrazyl (DPPH), phương pháp gây độc và ức chế sự tăng sinh tế bào MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] kết quả cho thấy: Cao etyl axetat (SC.E), cao tổng (SC), cao ethanol - Nước (SCM) biểu hiện hoạt tính chống oxi hóa với giá trị SC50 lần lượt là 38,05 µg/ml, 48,03 µg/ml, 94,04 µg/ml. Mẫu SC, SC.E biểu hiện hoạt đối với dòng tế bào ung thư Hep - G2 với giá trị IC50 lần lượt là 37,2 μg/ml và 18,9 μg/ml. Các mẫu còn lại hoạt tính yếu hoặc không có hoạt tính.
... The bioactive molecules can influence several cellular activities that modify the risk of various diseases. C. orchioides is a potent source of polyphenols, tannins, alkaloids, triterpenoids, glycosides, and flavonoids [19]. Besides, these various triterpenoid glycosides were isolated from the rhizomes [20]. ...
... This study showed that the methanolic extract of the C. orchioides exhibited cholinesterase inhibitory activity in both in vitro and in vivo conditions. A number of bioactive molecules have already been discovered from this plant having antioxidant and antiinflammatory activities [19,20]. There is a link between the presence of antioxidant and antiinflammatory agent with cholinesterase inhibitory activities [30]. ...
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, and one of the most predominant causes of dementia in older people. Preventing acetylcholine from breakdown by an excess amount of acetylcholinesterase is a proven therapy for AD. Traditionally Curculigo orchioides is known for its antioxidant activity, enzyme inhibition activity, and other medicinal uses. In this study, in vitro acetylcholinesterase, inhibitory activity was investigated, and methanolic extract of the plant showed significant activity. This study aims to investigate cholinesterase inhibitory activity, learning, and memory-enhancing activity of Curculigo orchioides. Materials and Methods: The crude methanol extract of the dried powder was prepared by the cold extraction method. In-vitro acetylcholinesterase (AChE) inhibitory activities were determined by the modified Ellman’s method. To confirm learning and memory-enhancing effects, the scopolamine-induced memory impairment Swiss-albino mice were used, and to find the anti-amnesic effect of the extract, a passive shock avoidance task was applied. Results: Results proved that scopolamine-induced cognitive dysfunction decreased significantly by administration of the plant extract solution in the passive avoidance task, and inhibited brain acetylcholinesterase activity. While running an in-vitro AChE inhibitory test the IC50 was 0.782±0.067μg/ml. Conclusion: The results suggested that methanolic extract of Curculigo orchioides can inhibit AChE in-vitro. Besides this, it provides data that proves its ability to improve whole brain AChE activity and enhance memory.
... The extract of C. orchioides restored levels of anti-oxidant enzymes of SOD, CAT, and GST, and significantly decreased the lipid peroxidation in the rat liver induced by Chromium (VI) treatment [66]. In the experiments performed by Hejazi et al. (2018), the ethylacetate fraction (EA) of C. orchioides exhibited significant radical scavenging activity on a DPPH assay with the IC 50 as 52.93 µg/mL; C. orchioides also refurbished the anti-oxidant enzyme defense of mammalian tissue during oxidative stress. EA and aqueous ethylacetate (AEA) fraction effectively inhibited the growth of tumor cell lines of HepG2, HeLa and MCF-7, down-regulated the levels of antiapoptotic Bcl-2 expression, and up-regulated the expression of apoptotic proteins caspase-3 and caspase-8 through an intrinsic ROS-mediated mitochondrial dysfunction pathway [67]. ...
... In the experiments performed by Hejazi et al. (2018), the ethylacetate fraction (EA) of C. orchioides exhibited significant radical scavenging activity on a DPPH assay with the IC 50 as 52.93 µg/mL; C. orchioides also refurbished the anti-oxidant enzyme defense of mammalian tissue during oxidative stress. EA and aqueous ethylacetate (AEA) fraction effectively inhibited the growth of tumor cell lines of HepG2, HeLa and MCF-7, down-regulated the levels of antiapoptotic Bcl-2 expression, and up-regulated the expression of apoptotic proteins caspase-3 and caspase-8 through an intrinsic ROS-mediated mitochondrial dysfunction pathway [67]. ...
The genus Curculigo, as a folk herbal medicine, has been used for many years in China, treating impotence, limb limpness, and arthritis of the lumbar and knee joints. The last systematic review of the genus Curculigo was written in 2013, scientifically categorizing the phytochemistry and biological activities. Hitherto, the original compounds and their pharmacological activities were presented as the development of this genus, but there is not an updated review. To conclude the progression of the genus Curculigo, we collected the new literature published from 2013 to 2021 in PubMed, Web of Science, Google Scholar databases, and the Chinese National Knowledge Infrastructure. The novel chlorophenolic glucosides, curculigine, phenolic glycosides, orcinosides and polysaccharides were isolated from Curculigo. The new analyzing methods were established to control the quality of Curculigo as a herbal medicine. In addition, the pharmacological effects of Curculigo focused on anti-diabetes, antibacterial, anti-inflammatory, osteoporosis, antioxidation, etc. The antitumor and neuroprotective activities were newly explored in recent years. The application of herbal medicine was gradually developed in scientific methods. The medicinal value of the genus Curculigo needs to further investigate its pharmacological mechanisms. This new review offers more insights into the exploitation of the pharmacological value of the genus Curculigo.
... ROS controls both physiological and pathological process related to cell proliferation, invasion cell, and tumour hypoxia and drug resistance [11,12,26,27]. Also, in the cell, a defence system against ROS includes several enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase [28]. However, when the cellular antioxidant systems are damaged, antioxidants are insufficient to neutralise ROS, and then oxidative stress occurs [27,29]. ...
... Other compounds related with their oxidant capacity and ROS productions are listed in Table 1. The antioxidants that are most well-known, curcumin, resveratrol and gallic acid, have activity against cancer cell line in vitro [15,24,28,35]. For example, galangin is a flavonoid with various biological effects in different cancer cells [25]. ...
... Te macromolecules SOD (PDB ID: 4MCM) [21], GPX (PDB ID: 3KIJ) [22], CAT (PDB ID: 1DGB) [23], COX-2 (PDB ID: 5IKT) [24], CDK-2 (PDB ID: 3QTR) [25], and EGFR (PDB ID: 1M17) [26] were chosen as the macromolecular targets for the docking studies. Tis selection was based on their established roles as potent molecular mediators and regulators of their respective biological functions. ...
Rhizophoramucronata Lam., a plant with a rich history of traditional use in various cultures, was subjected to chemical investigation, resulting in the isolation of five terpenoids and derivatives. The structures of these compounds, namely, 1,1,5,7-tetramethyl-4,5-dihydroacenaphthylen-3(1H)-one (1), 3β-hydroxy-11-oxo-olean-12 enyl palmitate (2), taraxerol (3), 3-(Z)-coumaroyltaraxerol (4), and 3β-(E)-coumaroyltaraxerol (5), were elucidated through extensive NMR spectroscopic analysis like ¹H NMR, ¹³C NMR, COSY, HSQC, and HMBC, as well as comparison with those of similar compounds described in the literature. These phytochemicals were subjected to computational assessment through molecular docking against superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and cyclin-dependent kinase 2 (CDK-2), in addition to ADME/T analyses. Molecular dynamics (MD) simulation was conducted for the compounds showing highest binding affinity toward respective receptor. Different fractions of the crude methanol (MeOH) extract were evaluated for their antioxidant, cytotoxicity, thrombolytic, and anti-inflammatory activities. The ethyl acetate soluble fraction (RME) exhibited the highest DPPH free radical scavenging activity, with an IC50 value of 1.73 μg/mL, compared to the standard (1.68 μg/mL). In the brine shrimp lethality cytotoxicity, the chloroform soluble fraction (RMC) and RME demonstrated substantial lethality, with LC50 values of 0.95 and 1.17 μg/mL, respectively, in comparison to the standard (0.35 μg/mL). Furthermore, the petroleum ether soluble fraction (RMP) and RME displayed substantial activity in the thrombolytic assay, with 86.12% and 73.12% clot lysis, respectively (p<0.001), compared to the standard (97.11%). In the membrane stabilizing assay, the RMC and RME exhibited significant inhibition of hypotonic solution and heat-induced hemolysis. The isolated compounds demonstrated impressive binding scores when interacting with SOD, GPX, CAT, and EGFR receptors. However, their performance was notably lacking when it came to binding with COX-2 and CDK-2 receptors.
... Interestingly, nano-hydroxyapatite (HA), the most widely used bone repair material with a similar calcium-phosphorus ratio to bone, has been reported to promote nerve differentiation and neuronal maturation [14,15]. More importantly, Curculigoside (CCG), a major natural compound extracted from the rhizomes of Curculigo orchioides Gaertn, exhibits a wide spectrum of biological activities such as anti-oxidation, anti-osteoporosis, nerve protection, pro-osteogenesis, and pro-angiogenesis [16][17][18][19]. However, the clinical application of this effective natural compound in the treatment of bone defects is limited by its low solubility, poor stability, short drug half-life, and excessive metabolic rate. ...
... The free binding energies were calculated using the AutodockVina program [99]. Results were compared with available literature data [100][101][102][103][104][105][106] to ensure the binding sites were appropriate for our study. The visualization was performed using the Biovia Discovery Studio visualizer. ...
Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC–ESI–QTOF–MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than Vaccinium corymbosum fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly (p < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo (p < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT2. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian Vaccinium corymbosum L.
... Orchioides thể hiện đáng kể hoạt tính loại bỏ tận gốc trong xét nghiệm DPPH với IC50 là 52,93 µg/ml [12]. Chiết xuất cồn của cây sâm cau có hoạt tính kháng khuẩn cao chống lại vi khuẩn Pseudomonas aeruginosa kháng methicillin, với giá trị MIC là 49 µg/ml, Bacillus cereus là 10,50 ± 0,5 mm, hoạt tính kháng nấm cao đối với Foc TR4 [4]. ...
Bài báo mô tả phân tích định tính, phân tích định lượng, đánh giá hoạt tính kháng khuẩn, hoạt tính chống oxy hóa của dịch chiết từ SC bằng phương pháp sắc ký lỏng cao áp (HPLC), phương Bertrand, Levanthal, Dược điển Việt Nam IV, Hoạt tính kháng vi sinh vật kiểm định được đánh giá bằng phương pháp Nồng độ Chất ức chế Tối thiểu (MIC), hoạt tính chống oxi hóa bằng phương pháp DPPH. Kết quả cho thấy: Sâm cau có chứa một số lớp chất hóa học như là: saponin, phytosterol, flanonoid, đường khử tự do, chất béo, alkaloid, carotene, tanin và axit hữu cơ… Hàm lượng đường khử tự do (10,7%), hàm lượng tinh bột (35,3%), hàm lượng cellulose (15,1%), hàm lượng tro (6,9%), hàm ẩm (9,1%) hàm lượng tanin (3,6%), hàm lượng saponin (19,8%), hàm lượng phytosterol (23,1%), hàm lượng flavonoid (4,3%), hàm lượng alkaloid (0,9%). Hoạt tính kháng vi sinh vật kiểm định cao tổng (CO) biểu hoạt tính kháng các chủng Escherichia coli, Bacillus subtillis, Fusarium oxysporum và Candida albicans với giá trị MIC 200 µg/ml. Cao COE ức chế các chủng Escherichia coli, Aspergillus niger và Fusarium oxysporum với giá trị MIC 200 µg/ml, ức chế chủng Bacillus subtillis với giá trị MIC 100 µg/ml. Cao COM ức chế các chủng Staphylococcus aureus và Candida albicans với giá trị MIC 200 µg/ml. Cao COE có hoạt tính chống oxi hóa trung bình với giá trị SC50 36,85 µg/ml, cao tổng CO với giá trị SC50 43,22 µg/ml và cao nước với giá trị SC50 90,54 µg/ml.
... The C. orchioides ethyl acetate and methanolic fraction have exhibited important antioxidant activities by scavenging free radicals. 46,47 The activity was studied in carbon tetrachloride (CCl 4 )-induced hepatopathy in rats, and it was found that the methanolic extract decreased the activity of antioxidant enzymes. 48 The 1,1-diphenyl-2-picrylhydrazyl and ferric reducing antioxidant power assay of the in vitro and in vivo plant extracts have suggested that both leaf and root extracts have potential antioxidant activity. ...
Curculigo orchioides , commonly called “Kali Musli,” is an endangered medicinal plant commonly found in Asian countries such as India, Japan, China, and Nepal. The plant holds a significant position in Ayurvedic and the Chinese traditional medicine system; it is documented as an aphrodisiac herb. The plant is also reported to be used in the treatment for asthma and jaundice. The botany, traditional uses, phytochemistry, and pharmacological activities to evaluate the plant's importance and relevant information are reviewed and summarized. We discern that a total of 61 phytochemicals are identified and reported in C. orchioides . These belong to the various phytochemical group of glycosides, lignans, polysaccharides, alkaloids, saponins, triterpenes, and aliphatic compounds. The most explored bioactive compound is a phenolic glycoside, curculigoside, isolated from the plant's rhizome. In vitro and in vivo research is conducted globally to provide primary and robust evidence to support this herbal medicine's traditional uses. A large lacuna regarding the mechanisms involved in the biological activity of the plant is evident. There is a need to conduct in-depth studies to understand the relationship between traditional and modern pharmacological uses of C. orchioides.
... species. Its rhizome extracts are used against antioxidative and anti-proliferative (Hejazi et al., 2018) and neuroprotective activity (Ramchandani et al., 2014). Therefore, in the present study, we have carried out the isolation of bioactive compounds from Indian C. orchioides Gaertn. ...
Alzheimer’s (AD) is one of the most common age-related neurodegenerative diseases in the world. Currently
it has affected about 33.9 million people and is estimated to triple over the next 5 years. The accumulation of
amyloid-beta plaques in the neurons is one of the important characteristic features of AD which leads to the
gradual decline of a person’s memory, learning and reasoning ability leading to difficulty in carrying out daily
activities. Medicinal plants are the main ingredients of native medicines and have a major role in traditional
health care. Of late, medicinal plants are being accepted widely because of fewer side effects compared to
synthetic drugs. Moreover, they also meet the requirement of medicine necessary for increasing human pop-
ulation. Medicinal plants play a crucial role in the development of new herbal drugs. Curculigo orchioides
Gaertn., commonly known as Kali Musli or golden grass, is extensively utilised as a nutritive tonic for
strength and treatment of asthma, skin diseases, neurodegenerative diseases, diarrhea, etc. To isolate and
characterize the MS-1 compound from Curculigo orchioides Gaertn.,rhizome. The isolated compound was
analysed by LC-MS, HPLC, FTIR, and 13 C &1 H��NMR and molecular docking studies. The neuroprotective
effect of the MS-1compound was evaluated on the Appl-GAL4 model of D.melanogaster. The MS-1compound
showed good neuroprotection, antioxidant activity and also increased the climbing activity and the lifespan
of Drosophila. These results might explain the effect of MS-1 compound as a good neuroprotective agent. In
the future, it can be used in making anti-Alzheimer drugs.
... In Chinese medicine, Curculigo orchioides Gaertn (COG, "Xian Mao"), it was applied topically for the management of knee and spine joints arthritis, leg fatigue and diarrhoea. COG seems to have antitumor effects and antioxidant, and could be employed as an antiosteoporotic herbal agent, according to latest research (Ramchandani et al., 2014;Vickers, 2017;Hejazi et al., 2018;Cui et al., 2019). COG has been studied in vivo for its antiosteoporotic activities in TCM for the management of postmenopausal women with osteoporosis. ...
According to World Health Organization (WHO), osteoporosis is a systematic bone disability marked by reduced bone mass and microarchitectural degeneration of osseous cells, which leads to increased bones feebleness and fractures vulnerability. It is a polygenetic, physiological bone deformity that frequently leads to osteoporotic fractures and raises the risk of fractures in minimal trauma. Additionally, the molecular changes that cause osteoporosis are linked to decreased fracture repair and delayed bone regeneration. Bones have the ability to regenerate as part of the healing mechanism after an accident or trauma, including musculoskeletal growth and ongoing remodeling throughout adulthood. The principal treatment approaches for bone loss illnesses, such as osteoporosis, are hormone replacement therapy (HRT) and bisphosphonates. In this review, we searched literature regarding the Traditional Chinese medicines (TCM) in osteoporosis and bone regeneration. The literature results are summarized in this review for osteoporosis and bone regeneration. Traditional Chinese medicines (TCM) have grown in popularity as a result of its success in curing ailments while causing minimal adverse effects. Natural Chinese medicine has already been utilized to cure various types of orthopedic illnesses, notably osteoporosis, bone fractures and rheumatism with great success. TCM is a discipline of conventional remedy that encompasses herbal medication, massage (tui na), acupuncture, food, and exercise (qigong) therapy. It is based on more than 2,500 years of Chinese healthcare profession. This article serves as a comprehensive review summarizing the osteoporosis, bone regeneration and the traditional Chinese medicines used since ancient times for the management of osteoporosis and bone regeneration.
... 14,15 It has been used to cure vomiting, kidney problems , leucorrhea, skin disease, asthma, bronchitis, jaundice, cancer, piles, leukoderma and also as aphrodisiac, antioxidant, antidiabetic, immunoadjuvant, antibacterial and neuroprotective. 16,17 The reported active bio-compounds are flavonoids, phenolic compounds, glycosides, alkaloids, saponins, and other secondary metabolites. 15,18 C. orchioides have been reported to contain many polyphenolic compounds such as curculigoside, a colourless, needle shaped polyphenol. ...
Since early ancient period human being are searching for new drugs with better therapeutic potentials. Traditional medicines are very important because it provide the right direction to the researcher to discover new plant based products against some specific problem and the knowledge has been passed through generation after generation. Curculigo orchioides Gaertn.and Asparagus racemosus Willd. both plants have immune stimulatory properties and are widely used by traditional healers for the treatment of various diseases. The main aim of the present study is to identify the secondary metabolites found in methanolic root extracts of C. orchioides and A. racemosus. Extraction was carried out through standard procedures and the analysis of plant extracts was carried out by using LC-ESI-MS/MS technique in positive and/or negative ionization mode. LC MS study tentatively identified 15 and 19 secondary metabolites from Curculigo orchioides and Asparagus racemosus respectively. Amongst these some were simple phenolic acids such as caffeic acid, quinic acid, p-coumaric acid, sinapic acid, protocatechuic acid, p-hydroxybenzoic acid and vanillic acid. Some others were phenolic acid esters such as chlorogenic acid, di caffeoylquinic acid, p-coumaroyl quinic acid and some flavonoids such as quercetin, rutin, kaempferol, catechin and apigenin were also tentatively identified. Two phenolics caffeic acid and caffeoyl hexoside were further confirmed by MS MS study. This study supports the ethnobotanical claims done by traditional healers of Purulia and Midnapore districts. Characterized phytochemicals were mainly phenolic and flavonoid compounds. Assured levels of phenolics along with other plant constituents in the studied plants supports the ethnobotanical claim done by traditional healers. Further research is needed on structural analysis and bioactivity assay of the identified compounds.
... Although the in vivo and in vitro extracts were not as efficient as ascorbic acid, the current finding suggests that in vivo AL and AR extracts have higher anti-oxidant activity when compared to in vitro extracts. Hejazi et al. (2018) found that the ethyl acetate extract of rhizomes had an IC 50 of 52.30 ± 66 µg mL −1 of DPPH, while the AL and AR in vivo extracts had IC 50 values of 438.9 ± 2.150 and 423.1 ± 2.615 µg mL −1 , respectively followed by high ferric reducing activity. ...
Curculigo orchioides (Kali Musli) is a medicinal plant commonly used in the Indian and Chinese traditional medicine system to treat jaundice and asthma. It is also used as an aphrodisiac in several countries. C. orchioides is treated as an essential resource in many pharmaceutical industries as a source of bioactive compounds. Indiscriminate use, depletion of its natural habitat, and its seasonal availability have resulted in its rarity. As per the IUCN status, Curculigo orchioides is now listed as an endangered plant. The present micropropagation study resolves its seasonal availability by ensuring a continuous supply of plants. In vitro somatic embryos were induced on the leaf explants of C. orchioides in one-fourth–strength Murashige and Skoog (MS) media. The embryos developed into whole plants in 8 wk. The in vitro plants produced were evaluated for their phytochemical evaluation and anti-oxidant activity along with their wild counterparts as controls. Both sets, wild plants termed in vivo and tissue-cultured plants called in vitro plants, were subjected to phytochemical extraction using a solvent gradient method. The extracts were analyzed qualitatively and quantitatively for phytochemical constituents. The anti-oxidant property of the extracts was screened using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and reducing power assays. The in vivo aqueous root extract (AR) and aqueous leaf extract (AL) had similar DPPH radical scavenging activity for both in vivo and in vitro plants. In vitro methanolic root extracts showed a significantly higher DPPH radical scavenging activity than other in vitro root extracts. The study demonstrates the medicinal properties of in vitro plants conclusively. It could be effectively used as an alternative, time-saving method for sustainable, season-independent usage of endangered plants for extraction while conserving and protecting their diversity and habitat in nature.
... In Ayurvedic system, it is specially used as a potent adaptogen and aphrodisiac medicine [90]. The medicinal plant has demonstrated a wide spectrum pharmacological activity, including antistress [91], immunostimulatory [92], hepatoprotective [93], antirheumatic [94], antihistaminic [95] and antiasthmatic [96], anti-inflammatory [97,98], analgesic [99], antioxidant and anticancerous [100] activity. The rhizome of Curcuma amada Roxb, commonly known as mango ginger due to its characteristic raw mango aroma, is used as an appetizer, antipyretic, aphrodisiac and laxative in Ayurveda system of medicine [101]. ...
Chhattisgarh state is situated in the central part of India and is also known as the ‘Bowl of rice’. Paddy is the principal crop of this state, and rice is the staple diet of the people. The state largely maintains its ethnic food culture as most of its population continues to live within rural and tribal areas. The state has nearly 44% of forest cover which serves as a decent source of food. People here prefer a vegetarian diet, and over 70 varieties of leaves, 25 varieties of tubers and roots are used here as vegetables. The present article is an attempt to explore the ethnic food culture of Chhattisgarh and to provide information about rice and non-rice-based traditional recipes, sweet dishes, leafy vegetables, tubers and roots which are consumed here. Irrespective of all the modern changes in food habits, the people of Chhattisgarh still preserve their traditional food culture.
... in PyRx 0.8. [10]. The docking was performed utilizing receptor proteins required with cell cycle, cell development, and DNA replication, i.e., cyclin-subordinate protein kinase 2 (CDK-2), CDK-6, DNA topoisomerases I and II, B-cell lymphoma 2 (Bcl-2), vascular endothelial development factor receptor 2 (VEGFR-2), and the telomere: G-quadruplexes. ...
Purpose: The human cytochrome P450 3A4 (CYP3A4) is the biggest individual from the CYP3A subfamily and records for 30–60% of the total for CYP450 adult liver. Hereditary varieties in CYP3A4 are a noteworthy hotspot for inter-patient changeability in plasma concentration, adverse effects and pharmacological response to medications. This research was done to discover naturally occurring novel CYP3A4 inhibitors from flavonoids. Methods: The molecular docking method was used to optimize the inhibiting activity of flavonoids against CYP3A4. PyRx Virtual Screening Tool 0.8 and BIOVIA Discovery Studio 2019 was used for simulation. Results: Flavonoids like Pongamoside A, Pongamoside B, and Pongamoside D have more binding affinity (kcal/mol) i.e. -11.6, -10.9, -10.8 respectively than Doxorubicin which have -10.7 against CYP3A4. Although, Daidzein, Genistein, and Luteolin form more hydrogen bonds than doxorubicin. Conclusion: The rational synthesis of natural analogues in reference to synthetic drugs, could generate drugs with improved therapeutic effect for chemoprevention. CYP3A4 plays a major role in the metabolism of various drugs; by the help of flavonoids, we can control the selective drug metabolism by inhibiting CYP3A4. Despite this, these molecules are not marketed for cancer treatment because of high polarity. If we could overcome this problem, these molecules can acts as effective anticancer agents in the future. Still, if we want to use these compounds clinically, there is a need to generate more scientific evidence and quality data by using in vivo and in vitro models. © 2020 iGlobal Research and Publishing Foundation. All rights reserved.
... Hence, herbal remedies are not in contrast with the functioning of conventional drugs. This authorizes herbal medications not only to have beneficial pharmacology, but also gives them the potential to have lesser side effects than conventional drugs (Hejazi et al., 2018). ...
World is familiar with the viral pathogen Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2). The principle working enzymes of SARS CoV-2 have been identified as main proteases 3Cl pro which act as main regulators for SARS infection. The need for therapy is required immediately pertaining to the vulnerable conditions. Protein-ligand studies are imperative for understanding the functioning of biological interactions as they are crucial in providing a hypothetical origin for the design and unearthing of novel drug targets. Phytoconstituents from Glycyrrhiza glabra, earlier reported to be anticancerous in nature were used as repurposed drugs against SARS CoV-2 main protease 3Clpro. We analyzed the molecular interactions of protein-phytocompounds, by AutoDock Vina 4.2 tools. The best interactions of each algorithm were subjected to molecular dynamic (MD) simulations to have an insight of the molecular dynamic mechanisms involved. Selected phytoconstituents gave a good score for binding affinity with the main protease 6LU7 of SARS CoV-2 as compared to the antiviral drugs already being used in the disease therapy. DehydroglyasperinC(-8.7,-8.1,-6.7,-7.1)kcal/mol, Licochalcone D(-8.4,-8.2,-7.1,-7.9) kcal/mol, Liquiritin(-8.6,-9.0,-7.2,-7.8) kcal/mol have showed energy interactions with 3Clpro better than many FDA approved repurposed drugs; Remdesvir, Favipiravir, and Hydroxychloroquine. MD Simulation also corelates our findings for molecular docking studies.
... From the western blot analysis, it has been shown that Hela, HepG2 and MCF-7 cell when exposed to plant extract there was a decrease in the expression of Bcl-2 protein, which is a antiopoptoptic protein, whereas the caspase-3 and caspase-8 expression is upregulated. Through the upregulation of caspase-3 and caspase-8 and downregulation of Bcl-2 proteins C. orchioides shows anti-cancerous properties [51]. ...
As a key component of plants, phytochemicals have significant
bioactivities regulating the biochemistry and metabolism of animals. This
field is being broadly studied for their ability as potential contributors to
the welfare of health. It is essential to build up scientific thinking to stop
their manipulation in foods since it’s a significant nutrient. These
phytochemicals have the following functions [1] cofactors for enzymatic
reactions [2] substrates for biochemical reactions [3] inhibitors in
enzymatic reactions [4] scavenging agent of many toxic and reactive
chemicals [5] increase the stability and absorption of considerable nutrients
[6] fermentation substrates for the essential intestinal, gastric and oral bacteria. Alkaloids, phenolics, fiber and terpenoids are the potential
phytochemicals of interest. Research has proved their significant role
against coronary heart disease, chronic inflammation, cancer, diabetes,
Alzheimer disease, various viral, parasitic and microbial infections, boils,
arthritis, itching, psychotic disease, ulcer, infertility related problems,
spasmodic conditions etc. Prevention has always been considered as a
significant strategy rather than cure and rehabilitation of the chronic
diseases. Significant sources that contain these bioactive
phytoconstituents, play a decisive role in prevention of chronic diseases.
... Curculigo orchioides Gaertn is a traditional herb listed in Pharmacopeia of China (2015 edition) (27), which has been used to enhance kidney yang, strengthen bones and muscles, and alleviate coldness and wetness in the body in China for many centuries (28). A recent study also reported that the extracts from the rhizomes of the plant Curculigo orchioides Gaertnits exhibited potent antioxidant activities (29). Curculigoside is a major active constituent of Curculigo orchioides Gaertn and a number of previously published studies have revealed that curculigoside inhibits oxidative damage and I/R injury in mouse cortical neurons, rat calvarial osteoblasts and human umbilical vein endothelial cells (18,30,31). ...
The aim of the present study was to determine whether curculigoside protects against myocardial ischemia‑reperfusion injury (MIRI) and to investigate the underlying mechanisms. An in vitro model of hypoxia/reoxygenation (H/R) was established by culturing H9c2 cells under hypoxic conditions for 12 h, followed by reoxygenation for 1 h. Cell Counting kit‑8 and lactate dehydrogenase (LDH) assays were subsequently used to examine cell viability and the degree of cell injury. In addition, isolated rat hearts were subjected to 30 min of ischemia followed by 1 h of reperfusion to establish a MIRI model. Triphenyltetrazolium chloride (TTC) staining was performed to measure the infarct size. Furthermore, TUNEL staining and flow cytometry were employed to evaluate cell apoptosis. The opening of the mitochondrial permeability transition pore (MPTP) and changes in the mitochondrial membrane potential (ΔΨm) were assessed. Reverse transcription‑quantitative PCR and western blot analysis were performed to investigate the expression levels of mitochondrial apoptosis‑related proteins. Curculigoside pre‑treatment significantly improved cell viability, decreased cell apoptosis and LDH activity, and reduced the infarct size and myocardial apoptosis in vitro and ex vivo, respectively. Moreover, curculigoside markedly inhibited MPTP opening and preserved the ΔΨm. In addition, curculigoside significantly decreased the expression of cytochrome c, apoptotic protease activating factor‑1, cleaved caspase‑9 and cleaved caspase‑3. Notably, atractyloside, a known MPTP opener, abrogated the protective effects of curculigoside. On the whole, the present study demonstrated that curculigoside protected against MIRI, potentially by decreasing the levels of mitochondria‑mediated apoptosis via the inhibition of MPTP opening. Therefore, the results obtained in the present study may provide the theoretical basis for the future clinical application of curculigoside.
... Curculigo orchioides Gaertn (CO, "Xian Mao"), one of curculigo species, is used to relieve the symptoms of limb weakness, lumbar and knee joint arthritis, and diarrhea in Chinese medicine (Tan et al., 2019). Recent studies have found that CO also appears to have antioxidant properties and anticancer potential, and may be used as an antiosteoporotic herb (Cao et al., 2008;Ramchandani et al., 2014;Hejazi et al., 2018). ...
Osteoporosis is a bone disease characterized by increasing osseous fragility and fracture due to the reduced bone mass and microstructural degradation. Primary pharmacological strategies for the treatment of osteoporosis, hormone replacement treatment (HRT), and alendronate therapies may produce adverse side-effects and may not be recommended for long-term usage. Some classic and bone-specific natural Chinese medicine are very popularly used to treat osteoporosis and bone fracture effectively in clinical with their potential value in bone growth and development, but with few adverse side-effects. Current evidence suggests that the treatments appear to improve bone metabolism and attenuate the osteoporotic imbalance between bone formation and bone resorption at a cellular level by promoting osteoblast activity and inhibiting the effects of osteoclasts. The valuable therapies might, therefore, provide an effective and safer alternative to primary pharmacological strategies. Therefore, the purpose of this article is to comprehensively review these classic and bone-specific drugs in natural Chinese medicines for the treatment of osteoporosis that had been deeply and definitely studied and reported with both bone formation and antiresorption effects, including Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer (syn. Morinda officinalis F.C.How), Curculigo orchioides Gaertn., Psoralea corylifolia (L.) Medik Eucommia ulmoides Oliv., Dipsacus inermis Wall. (syn. Dipsacus asperoides C.Y.Cheng & T.M.Ai), Cibotium barometz (L.) J. Sm., Velvet Antler, Cistanche deserticola Ma, Cuscuta chinensis Lam., Cnidium monnieri (L.) Cusson, Epimedium brevicornum Maxim, Pueraria montana (Lour.) Merr. and Salvia miltiorrhiza Bunge., thus providing evidence for the potential use of alternative Chinese medicine therapies to effectively treat osteoporosis.
... Salt-processed C. orchioides (SXM) is an innovative technology designed by our research group, guided by the theories of traditional Chinese medicine of "Ru Yan Zou Shen" and "Xiang Fan Wei Zhi". These theories have thousands of history in clinical uses in China (Tao et al., 2017;Chen et al., 2018;Hejazi et al., 2018). Furthermore, wine-processing and salt-processing can reduce or remove the side-effects of C. orchioides, while also changing its properties and strengthening its efficacy. ...
This study was designed to explore the pharmacokinetic regularity of the plasma concentration, tissue distribution and excretion of orcinol glucoside from aqueous extracts of raw and processed Curculigo orchioides Gaertn., Hypoxidaceae. The experiment first used an ultrahigh-performance liquid chromatography-tandem mass spectrometry approach with multiple reaction monitoring and a positive mode to separate orcinol glucoside from naringin to obtain the plasma concentration curves, bar graph of tissue distribution and excretion curves. These results might be beneficial for reasonable clinical application of C. orchioides and for further development of its wine and salt-processing mechanism. Keywords: Excretion, Plasma concentration, Tissue distribution, Wine-processing technology
... Low concentrations of E2 inhibit tamoxifen-induced generation of reactive oxygen species ROS are important second messengers indispensable in several physiological processes (Ha et al., 2016). Specifically, human cancers arise when the redox balance is aberrant (Hejazi et al., 2018). ROS are also considered an important signal of apoptosis (Ghosh et al., 2010;Ha et al., 2016). ...
Tamoxifen has been applied widely in the treatment of estrogen receptor (ER)-positive breast cancer. The impact of low concentrations of 17β-estradiol (E2) (a pervasive environmental pollutant) on its effectiveness was studied in vitro using an MCF-7 cell line. Cell proliferation, migration, invasion, and apoptosis were studied along with cell cycle progression, reactive oxygen species generation and mitochondrial membrane potentials repression. The signaling pathways involved were identified. Typical concentrations of E2 in the environment (10−10 to 10−8 M) were observed to promote cell growth and protect MCF-7 cells from tamoxifen's cytotoxicity. Cell migration, invasion, cell cycle progression and apoptosis all involved in reducing tamoxifen's cytotoxicity. E2 at environmental concentrations induced PI3K/Akt and MAPK/ERK signal transduction through the estrogen receptor pathways to affect cell proliferation. Taken together, the results explain how E2 in the environment may attenuate the efficacy of tamoxifen in ER-positive breast cancer therapy. They provide considerable support for E2's adverse effects on human health and cancer management.
... ere are approximately 20 known species of Curculigo. Some of these species are said to have medicinal properties, such as acting as an anticancer agent and preventing gastrointestinal, cardiovascular, and heart-related diseases [15]. In our previous study, C. latifolia, which can be found in West Malaysia, was shown to exhibit antidiabetic properties in diabetic-induced rats. ...
This study aims to extract antioxidant compounds from Curculigo latifolia root by subcritical water extraction (SWE). The influence of extraction temperature and time on the antioxidant activity of C. latifolia root extract was investigated in terms of extraction yield, total phenolic content (TPC), total flavonoid content (TFC), 2, 2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The highest extraction yield (36.5%), TPC (92.55 mg GAE/g), TFC (13.26 mg RE/g), and antioxidant activities by ABTS (66.8 mg trolox equivalent/g sample) and DPPH (128.7 mg trolox equivalent/g sample) were detected at 180°C and 30 minutes extraction time. Based on the results, the optimum condition was selected at 180°C and 30 minutes of extraction. The sample was screened by using liquid chromatography-mass spectrometry (LC-MS) analysis where the phenolic compounds detected were structured based on their [M-H]-peak. The detected phenolic compounds were monobenzone, hydroquinone, phloridzin, pomiferin, mundulone, scandenin, and dimethyl caffeic acid. According to these findings, SWE is a promising, environmentally friendly, and efficient technology in the exploitation of natural products for the development of food and nutraceutical commodities.
... Previous research suggested that the rhizome of this plant was used in antioxidant, antibacterial and antifungal activity, hypoglycaemic, hepatoprotective activity, overcoming impotence, spasmolytic, aphrodisiac, diuretic, antipyretic, harmonizing the immune system, antitumor activity, antiproliferative, cytotoxic activity, anti-inflammatory and anticancerous principles 5,6,13,15,16,18,24,25,[31][32][33] . ...
Curculigo orchioides is an endangered medicinal herb belonging to the family Hypoxidaceae. Using MS medium supplemented with TDZ (0.03, 0.05, 0.07, 1 mg/l) and BAP (0.5, 1, 1.5 mg/l) alone or in combination with 0.05 and 0.1 mg/l NAA, in vitro shoot regenerations were tested from three different tissues (rhizome apical tip, rhizome, leaf) of C. orchioides. Result analysis found that shoot regeneration in MS medium supplemented with TDZ (0.07 mg/l) combination with NAA (0.1 mg/l) from rhizome apical tip of C. orchioides was significantly highest compared among treatment. In this treatment, 100 % cultures responded with an average number of 8.67 shoots per explant. Additionally, rooting per shoot regeneration in the half MS medium supplemented with 1.5 mg/l IBA was significantly highest. The rooted plants were successfully transplanted to soil with 100% success. Based on our results, we suggest that the best effect in vitro regeneration of C. orchioides may be to use MS medium supplemented with TDZ (0.07 mg/l) combination with NAA (0.1 mg/l) from rhizome apical tip tissue.
... 7 Cellular processes like generation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential are associated with the execution of the apoptosis pathways namely, extrinsic death receptor and intrinsic mitochondrial pathway. 8 Treating cancer by inducing apoptosis through various chemotherapeutics is one the most fascinating approach in cancer research, 9 however, many of these chemotherapeutic drugs lack efficiency due to the increased resistance. 10 Thus, sequential apoptotic cell death and its role in facilitating various effective anticancer agents have drawn substantial attention. ...
N‐benzhydrylpiperazine and 1,3,4‐oxadiazoles are pharmacologically active scaffolds which exhibits significant inhibitory growth effects against various cancer cells, however, antiproliferation effects and the underlying mechanism for inducing apoptosis for aforementioned scaffolds addressing HeLa cancer cells remains uncertain. In this study, N‐benzhydrylpiperazine clubbed with 1,3,4‐oxadiazoles (4a–4h) were synthesized, subsequently characterized using high resolution spectroscopic techniques and eventually evaluated for their antiproliferation potential by inducing apoptosis in HeLa cancer cells. The MTT assay screening results revealed that among all, compound 4d ( N‐benzhydryl‐4‐((5‐(4‐aminophenyl)‐1,3,4‐oxadiazol‐2‐yl)methyl)piperazine) in particular, exhibited IC 50 value of 28.13 ± 0.21 μg/mL and significantly inhibited the proliferation of HeLa cancer cells in concentration‐dependent manner. The in vitro anticancer assays for treated HeLa cells resulted in alterations in the cell morphology, reduction in colony formation, and inhibition of cell migration in concentration‐dependent treatment. Furthermore, G2/M phase arrest, variations in the nuclear morphology, degradation of chromosomal DNA confirmed the ongoing apoptosis in treated HeLa cells. Increase in the expression of cytochrome C and caspase‐3 confirmed the involvement of intrinsic mitochondrial pathway regulating the cell death. Also, elevation in reactive oxygen species level and loss of mitochondrial membrane potential signified that compound 4d induced apoptosis in HeLa cells by generating the oxidative stress. Therefore, compound 4d may act as a potent chemotherapeutic agent against human cervical cancer. We are reporting for the first time the underlying mechanism involved in apoptosis induction in HeLa cancer cells for structurally similar azole conjugates.
Cancer is undoubtedly a serious, appalling disease that epitomizes one of the most severe global life-threatening health issues for the human race in both developing and developed countries. Genetic mutations and epigenetic alterations play a significant role in the initiation of cancer. Literature suggests the involvement of inherited genetic mutations in 5–10% of all cancers, whereas the majority of the cancer cases are elicited by modern lifestyle and environmental factors that may epigenetically alter normal cellular growth, survival, and functioning. The fact sheets from the World Health Organization (WHO) have revealed truly astounding and alarming statistics, affirming approximately ten million deaths in 2020. This persuades the scientific community to develop a proactive approach to cancer treatment using naturally derived compounds with minimal systemic side effects to cure the affected individuals or prolong their lives substantially, assuring a good quality of life. The use of plant extracts or phytochemicals can offer a promising platform for the development of potent anticancer drugs as many of them are well known to exhibit their anticancer activities in numerous ways of molecular mechanisms of action, for instance, either targeting certain enzymes associated with cell cycle regulation, suppression of tumor cell-activating proteins, and inhibiting signaling pathways (PI3K, Akt, mTOR) or by inhibiting transcription factors. Nevertheless, scientific evidence has indicated various phytochemicals with chemopreventive properties and their efficacy on cancer proteins, enzymes, and multiple targeted cytotoxicity. Therefore, the epigenetic mechanisms of action of phytochemicals will undoubtedly help to identify the leads to reverse the early epigenetic modifications and exploit them as an effective strategy to prevent tumorigenesis. This chapter intends to analyze the role of phytochemicals for their epigenetic modifying potential in the functional regulation of tumorigenesis and provide technical support for evidence-based applications of phytochemicals in anticancer therapeutics.KeywordsCancerEpigeneticsPhytochemicalsCell signalingCancer Therapeutics
Objective
Dexamethasone, a synthetic glucocorticoid drug, is widely used as an anti-inflammatory/anti-allergic agent worldwide. Several previous studies suggested that in the inflammatory or enriched free radical condition, Dexamethasone directly binds to DNA leading to DNA breakage/remodeling and subsequently cancer or other DNA breakage-related disorders.Methods
So, for the first time, we computationally and experimentally investigated the interaction of the Dexamethasone drug, alone and in combination with H2O2, ascorbic acid, iron, and copper, with a routine supercoiled plasmid DNA. In the next step, the intrinsic DNA binding constant (kd) was calculated using UV absorption titration method via Dexamethasone interaction with calf thymus DNA (ctDNA). Also, the interaction of the drug with antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase 4, and glutathione reductase was investigated by molecular docking methods.ResultsInterestingly, our in-vitro study demonstrated that dexamethasone binds to DNA by binding energy of −5.35 kcal/mol. Our study also indicated that dexamethasone/DNA interaction leads to no DNA breakage while its combination with the mineral supplies causes DNA damage/breakage. These results are consistent with our Docking study that indicated dexamethasone strongly binds to DNA and the catalytic site of glutathione peroxidase 4, the FAD-binding site of the glutathione reductase, the active site of the superoxide dismutase, and NADPH binding residues of the catalase enzyme. Conclusions
Therefore, we hypothesize that Dexamethasone may indirectly cause DNA damage by inhibiting antioxidant defense enzymes and causing oxidative stress in cells.
Ethnopharmacological relevance:
Jinfeng Pill (JFP) is a classical Chinese medicine formula and composed of 9 herbs, including Epimedium brevicornu Maxim (Yinyanghuo), Cervus elaphus Linnaeus (Lurong), Panax ginseng C.A.Mey. (Renshen), Equus asinus (EJiao), Ligustrum lucidum W.T.Aiton (Nvzhenzi), Reynoutria multiflora (Thunb.) Moldenke (Heshouwu), Curculigo orchioides Gaertn (Xianmao), Neolitsea cassia (L.) Kosterm. (Rougui) and Leonurus japonicus Houtt. (Yimucao). The formula is clinically used to regulate menstrual cycle and alleviate polycystic ovarian syndrome due to its capabilities of ovulation induction. It is therefore presumed that JFP could be used for the therapy of premature ovarian insufficiency (POI) but the assumed efficacy has not been fully substantiated in experiment.
Aim of study:
To evaluate the effectiveness of JFP on cyclophosphamide (CTX)-induced POI and preliminarily explore its potential mechanisms of action.
Material and methods:
An experimental rat model of POI was established by using CTX induction to assess the efficacy of JFP. The potential targets of action for JFP alleviating POI were predicted by the combination of network pharmacology and transcriptomics and finally validating by RT-qPCR and Western blot.
Results:
JFP alleviated the damages of ovarian tissue induced by CTX in the rat model of POI via significantly decreasing serum levels of FSH and LH and the ratio of FSH/LH and increasing the levels of E2 and AMH, accompanied with promoting ovarian folliculogenesis and follicle maturity and reversing the depletion of follicle pool. With the analysis of network pharmacology, pathways in cancer, proteoglycans in cancer, PI3K-AKT, TNF and FoxO signaling pathways were predicted to be influenced by JFP. The results of RNA-seq further revealed that IL-17 signaling pathway was the most important pathway regulated by both CTX and JFP, following by transcriptional misregulation in cancer and proteoglycans in cancer. Combining the two analytical methods, JFP likely targeted genes associated with immune regulation, including COX-2, HSP90AA1, FOS, MMP3 and MAPK11 and pathways, including IL-17,Th17 cell differentiation and TNF signaling pathway. Finally, JFP was validated to regulate the mRNA expression of FOS, FOSB, FOSL1, MMP3, MMP13 and COX-2 and decrease the release of IL-17A and the protein expression of IL-6 and suppress the phosphorylation of MEK1/2 and ERK1/2 in CTX induced POI rats.
Conclusion:
Jinfeng Pill is effective to ameliorate the symptoms of POI induced by CTX in the model of rats and its action is likely associated with suppressing IL-17A/IL-6 axis and the activity of MEK1/2-ERK1/2 signaling.
The immune system plays a crucial role in regulating osteoclast formation and function and has significance for the occurrence and development of immune-mediated bone diseases. Kidney-tonifying Chinese herbs, based on the theory of traditional Chinese medicine (TCM) to unify the kidney and strengthen the bone, have been widely used in the prevention and treatment of bone diseases. The common botanical drugs are tonifying kidney-yang and nourishing kidney-yin herbs, which are divided into two parts: one is the compound prescription of TCM, and the other is the single preparation of TCM and its active ingredients. These botanical drugs regulate osteoclastogenesis directly and indirectly by immune cells, however, we have limited information on the differences between the two botanical drugs in osteoimmunology. In this review, the mechanism by which kidney-tonifying Chinese herbs inhibiting osteoclastogenesis was investigated, emphasizing the immune response. The differences in the mechanism of action between tonifying kidney-yang herbs and nourishing kidney-yin herbs were analysed, and the therapeutic value for immune-mediated bone diseases was evaluated.
p> Curculigo orchioides Gaertn. is used in traditional medicine in Vietnam. The antioxidant potential of Curculigo orchioides was evaluated through DPPH radical scavenging and total antioxidant capacity method. The data resulted from DPPH radical scavenging activities indicated that Curculigo orchioides displayed the good activities with low IC50 value (22.78μg/mL), approximately 1.5 times less than that of curcumin (34.34 μg/mL). The total antioxidant capacity of the extract of Curculigo orchioides contained 132.48 ± 1.48 mg GA/g or 264.45 ± 2.34 μmol AS/g. Content of compounds from Curculigo orchioides including the total phenolic, total flavonoid, polysaccharides, and saponin - triterpenoids were examined using the colorimetric method with reagents. The content of phenolic compounds, flavonoid compounds, polysaccharides, and saponin – triterpenoids found in Curculigo orchioides was 196.24 ± 1.45 mg GAE/g, 78.49 ± 1.78 mg QUE/g, 4.34 ± 0.08 %, 47.60 ± 0.24 mg Rb1/g (Rb1: (Gypenoside III)), respectively. Specifically, the total saponin - triterpenoid content of Curculigo orchioides has been reported for the first time.</p
Curculigo orchioides (CUR) and Epimedium (EPI) are traditional Chinese medicines with estrogen-like biological activity, called Xianmao and Xianlingpi (Er-xian) in Chinese. However, whether Er-xian exerts protective effects on myocardial ischemia-reperfusion injury (MIRI) is unknown. This study aimed to investigate the cardioprotective effects of Er-xian preconditioning against MIRI and the underlying mechanisms. CUR or EPI was administered intragastrically to aged female rats as a monotherapy or combination therapy. 2 weeks later, a rat MIRI model was established. Myocardial infarction size, myocardial morphology, cTnT, cell apoptosis rate, intracellular calcium concentration, mitochondrial permeability transition pore (MPTP) opening and reperfusion injury salvage kinase (RISK) signaling pathway molecules were observed after the surgery. To evaluate the mechanisms of Er-xian, estrogen receptors antagonists ICI 182780 and G15 were used. In this study, Er-xian notably alleviated myocardial tissue damage, maintained mitochondrial morphology, reduced infarct size and cardiac markers, and increased sera levels of E2. Moreover, Er-xian inhibited calcium overload and mPTP opening, and decreased cardiomyocyte apoptosis. We found that the dual therapy of CUR and EPI elicited more noticeable results than CUR or EPI monotherapy. The significant protective effects of Er-xian on ischemia-reperfusion myocardium were attributed to the up-regulation of AKT, ERK1/2 and GSK-3β phosphorylation levels. The cardioprotective effects of Er-xian were significantly reduced after estrogen receptor blockade, especially GPER30. These results indicate that Er-xian attenuates MIRI through RISK signaling pathway and estrogen receptors are the critical mediators.
Dexamethasone, a synthetic glucocorticoid drug, is widely used as an anti-inflammatory/anti-allergic agent worldwide. Several previouse studies suggested that in the inflammatory or enriched free radical condition, Dexamethasone directly bind to DNA leading to DNA brekage/remodeling and subsequently cancer or other DNA breakage related disorders. So, for the first time, we computationally and experimentally investigated the interaction of Dexamethasone drug, alone and in combination with H 2 O 2 , ascorbic acid, iron and copper, with a routine supercoiled plasmid DNA. In the next step, the intrinsic DNA binding constant (k d ) was calculated using UV absorption titration method via Dexamethasone interaction with calf thymus DNA (ctDNA). Also, interaction of the drug with antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase 4, glutathione reductase was investigated by molecular docking methods. Interestingly, our in-vitro study demonstraded that dexamethasone binds to DNA by binding energy of -5.35 kcal/mol. Our study also indicatd that dexamethasone/DNA interaction lead to no DNA breakage while, its combination with the mineral supplies cause to DNA damage/breakage. This results are consistent with our Docking study that indicated dexamethasone stungly bind to DNA and the catalytic site of glutathione peroxidase 4, FAD-binding site of the glutathione reductase, the active site of the superoxide dismutase and NADPH binding residues of the catalase enzyme. Therefore, we hypothesis that Dexamethasone may indirectly make DNA damages by inhibiting antioxidant defense enzymes and causing oxidative stress in cells.
Introduction
Chronic myeloid leukemia (CML) is a myeloproliferative hematological malignancy wherein the increased relapsed cases and lack of drug effectiveness generates a need to identify an effective treatment regimen. A unani formulation, Habb-e-Asgandh (HEA) is being used for treatment of ailments such as arthritis, however, its role in CML therapeutics has not been reported yet. Hence, anti-leukemic efficacy of HEA was assessed alone or in combination with standard chemotherapeutic, imatinib in CML cell line K562.
Methods
The anti-leukemic effect of HEA was evaluated on cell cytotoxicity by MTT assay, cell cycle analysis by propidium iodide staining, apoptotic assay by Annexin-V assay, mitochondrial membrane potential (MMP) by JC1 staining. Further, effect of drug treatment on oxidative stress and cell migration was determined by ORAC assay and transwell migration assay respectively. Lastly, changes in angiogenic marker (VEGF) and inflammatory marker (IL-6) were examined by ELISA.
Results
HEA induced cytotoxicity of leukemic cells which increased further when co-treated with imatinib. The combinatorial treatment of HEA with imatinib potentiates anti-tumor effect by inducing cell apoptosis with disruption of MMP even at low concentrations. Subsequent studies revealed that tumor killing property of HEA increased the ROS generation. Furthermore, HEA in combination with imatinib dramatically reduced cell migration along with expression of VEGF and IL-6.
Conclusion
This maiden study demonstrated that HEA possesses anti-leukemic potential in vitro. This formulation potentiates the effect of imatinib even at low concentrations suggesting the utilization of HEA as a novel adjuvant therapy for the better management of CML in future.
Correct species identification is crucial for ensuring the quality, safety, and efficacy of herbal medicine. Market research indicates that Curculigo glabrescens Rhizoma (CGR) was the major counterfeit of the medicine Curculigo orchioides Rhizoma (COR). To accurately discriminate COR and CGR remains a challenge, and it becomes even more difficult when the herbs have been heavily processed into a powder. In this work, combined with high performance liquid chromatography analysis, a novel component in CGR was discovered, and two stable isotopes (N%, C%, δ15N, δ13C) and nineteen mineral elements were determined along with multivariate statistical analysis to distinguish the authentic COR samples and counterfeit CGR samples. The results showed that there were significant differences between the mean value of N%, δ15N and δ13C according to the botanical origins. In addition, these two species can be differentiated by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) analysis. A linear discriminant analysis (LDA) model with a good classification rate (100%) and cross-validation rate (100%) was established. Hence, stable isotope and mineral element contents combined with chemometrics analysis could be considered as an effective and reliable method for discriminating the source species of COR and CGR.
Ethnopharmacological relevance
The plants of genus Curculigo are divided into the Section Curculigo and the Section Capitulata, which are mainly distributed in southeastern and southwestern China. Various ancient chinese books record that these plants were used as an important herb for tonifying kidney yang. Traditional Chinese medicine often draws on this property to treat depression syndrome. Thus genus Curculigo has potential for the treatment of neurodegenerative diseases (ND). The study showed that phenolics were the main characteristic components of plants in the Section Curculigo, represented by orcinol glucoside and curculigoside; the norlignans, with Ph-C5-Ph as the basic backbone, were the main characteristic components of the Section Capitulata. However, there is a lack of sufficient scientific evidence as to whether these two types of ingredients have neuroprotective effects.
Aim of the study
To determine the neuroprotective effects of phenolics and norlignans in genus Curculigo on human neuroblastoma cells SH-SY5Y. To discuss their structure-activity relationship and screen for compounds with high activity and neuroprotective effects. To reveal that the amelioration of endoplasmic reticulum (ER) stress by two classes of compounds is mediated by the PERK/eIF2α/ATF4 pathway.
Materials and methods
The cytotoxicity of 17 compounds was assayed by MTT. SH-SY5Y cells were damaged by corticosterone (Cort) (200 μM) for 24 h and then co-administered with 17 compounds (0.1–100 μM) and Cort (200 μM) for 24 h. Cell survival was determined by MTT assay. Apoptosis rate, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels were detected using flow cytometry. Intracellular Ca²⁺ levels were detected using a fluorescent probe. Cellular mitochondrial and ER damage was observed using transmission electron microscopy (TEM). ER stress and apoptotic pathway-related proteins (BiP, CHOP, cleaved caspase-3, cleaved caspase-9, Bax/Bcl-2), and the expression level of PERK/eIF2α/ATF4 pathway was measured via western blot (WB).
Results
The experimental data showed that Cort treatment of SH-SY5Y cells resulted in decreased cell survival and increased apoptosis, mitochondrial depolarization, ROS, and intracellular Ca²⁺ levels. The co-action of 17 compounds and Cort for a period of time significantly increased cell survival. Compounds 3, 7, 12, 13 also reduced apoptosis rate, mitochondrial depolarization, ROS and intracellular Ca²⁺ levels in the subsequent experiments. In addition, TEM observed that Cort caused mitochondrial and ER damage, and the damage was improved after treatment. WB analysis obtained that Cort increased the expression of apoptotic and ER stress-related proteins and activated pathway expression. However, in the presence of compounds 3, 7, 12, 13, the expression of BiP, CHOP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 was significantly reduced, and the phosphorylation of PERK and eIF2α and the expression of ATF4 were inhibited.
Conclusion
This study found that one phenolic (3) and three norlignans (7, 12, 13) from genus Curculigo have significant neuroprotective effects. The results of the structure-activity relationship indicated that the glucosyl polymeric norlignans and the phenolics with benzoic acid as the parent nucleus were more active. The neuroprotective effect of three norlignans is the latest discovery. This finding has important research value in the field of prevention and treatment of neurodegenerative diseases.
Tibial dyschondroplasia (TD) is a metabolic tibiotarsal bone disease in rapidly growing birds throughout the world, which is characterized by gait disorders, reduced growth, and in an unrecoverable lameness in many cases. The short production cycle in chickens, long metabolism cycle in most of the drugs with the severe drug residue, and high treatment cost severely restrict the enthusiasm for the treatment of TD. Traditional Chinese medicine (TCM) has been used for the prevention, treatment, and cure of avian bone diseases. Previously, a couple of traditional Chinese medicines has been reported being useful in treating TD. This review will discuss the TCM used in TD and the alternative TCM to treat TD. Selecting a TCM approach and its pharmacologic effects on TD chickens mainly focused on the differentiation, proliferation, and apoptosis of chondrocytes, angiogenesis, matrix metabolism, oxidative damage, cytokines, and calcification of cartilage in tibia.
Background: Market research found that Curculigo glabrescens Rhizoma (CGR) is the major counterfeit of the Curculigo orchioides Rhizoma (COR). C. orchioides Gaertn and C. glabrescens (Ridl.) Merr. belong to the same family and genus, with close plant relationships and high genetic similarity, and rhizomes of the herbs part have less distinguished characteristics, which make the identification difficult.
Methods: In order to distinguish COR from CGR more accurately and conveniently, HPLC method was used to establish a characteristic chromatogram of the two herbs, and a unique component in CGR was discovered for first time. Based on that, the characteristic component was systematically separated and purified.
Results: The unique component was a new neolignans and named glabrescenin, which could specifically distinguish COR from CGR. The HPLC method we used could establish a characteristic chromatography of CGR.
Conclusion: This study was conducive to the quality control of Curculigo, and could promote the correct application of genuine COR in clinical practice.
p> Curculigo orchioides Gaertn. is used in traditional medicine in Vietnam. The antioxidant potential of Curculigo orchioides was evaluated through DPPH radical scavenging and total antioxidant capacity method. The data resulted from DPPH radical scavenging activities indicated that Curculigo orchioides displayed the good activities with low IC50 value (22.78μg/mL), approximately 1.5 times less than that of curcumin (34.34 μg/mL). The total antioxidant capacity of the extract of Curculigo orchioides contained 132.48 ± 1.48 mg GA/g or 264.45 ± 2.34 μmol AS/g. Content of compounds from Curculigo orchioides including the total phenolic, total flavonoid, polysaccharides, and saponin - triterpenoids were examined using the colorimetric method with reagents. The content of phenolic compounds, flavonoid compounds, polysaccharides, and saponin – triterpenoids found in Curculigo orchioides was 196.24 ± 1.45 mg GAE/g, 78.49 ± 1.78 mg QUE/g, 4.34 ± 0.08 %, 47.60 ± 0.24 mg Rb1/g (Rb1: (Gypenoside III)), respectively. Specifically, the total saponin - triterpenoid content of Curculigo orchioides has been reported for the first time.</p
Tamoxifen was widely applied in the therapy of estrogen receptor (ER)‐positive breast cancer. With the purpose of determining the potential impacts of quercetin on its effectiveness, MCF‐7 cells were selected as the in vitro model and several cellular biological behaviors (ie, cell proliferation, migration, invasion, cycle, apoptosis, and oxidative stress) were investigated. As results, quercetin showed contrasting dose‐response to cellular behaviors dependent on the ROS‐regulated p53 signaling pathways. In detail, quercetin promoted cell proliferation and inhibited cell apoptosis at low concentrations, whereas high‐concentration resulted in apoptosis induction. Moreover, quercetin at a low concentration significantly inhibited tamoxifen‐induced antiproliferation in MCF‐7 cells, whereas high concentrations enhanced cell apoptosis in a synergetic manner. The real‐time quantitative polymerase chain reaction analysis further implied that quercetin exerted its dual roles in tamoxifen‐induced antiproliferative effects by regulated the gene expression involved in cell metastasis, cycle, and apoptosis through the ER pathways. Our present study provides a considerable support to the combination of quercetin and tamoxifen on human ER‐positive breast carcinoma management.
Piperazine scaffolds or 2-Azetidinone pharmacophores have been reported to show anti-cancer activities and
apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of
apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study
emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these
structurally related azoles derivatives in HeLa cancer cells. 1-phenylpiperazine clubbed with 2-azetidione
derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in
-vitro anti-proliferative activities and induction of apoptosis. Further, we also evaluated oxidative stress generated
by these synthetic derivatives (5a-5h). Cell viability studies revealed that among all, the compound N-(3-chloro-2-
(3-nitrophenyl)-4-oxoazetidin-1-yl)-2-(4-phenylpiperazin-1-yl) acetamide 5e remarkably inhibited the growth of
HeLa cells in a concentration dependent manner having IC50 value of 29.44±1.46 µg/ml. Morphological changes,
colonies suppression and inhibition of migration clearly showed the antineoplasicity in HeLa cells treated with 5e.
Simultaneously, phosphatidylserine externalization, DNA fragmentation and cell-cycle arrest showed ongoing
apoptosis in the HeLa cancer cells induced by compound 5e in concentration dependent manner. Additionally,
generation of intracellular ROS along with the decrease in mitochondrial membrane potential supported that
compound 5e caused oxidative stress resulting in apoptosis through mitochondria mediated pathway. Elevation in
the level of cytochrome c and upregulation in expression of caspase-3 clearly indicated the involvement of the
intrinsic pathway of programmed cell death. In brief; compound 5e could serve as a promising lead for the
development of an effective antitumor agent.
Recurrence is one of the major causes of high mortality in ovarian cancer. However, the mechanism of ovarian cancer recurrence after chemotherapy has not been fully understood. In the present study, we investigated the effect of chemotherapy-induced tumor microenvironment on the proliferation of SKOV3 cells. We have shown that SKOV3 cells repopulated faster in the culture medium from apoptotic SKOV3 ovarian cancer cells after 24 h of etoposide phosphate (VP-16) treatment. We found that during apoptosis, cleaved caspase 3 could activate cytosolic calcium-independent phospholipase A2, which stimulated the release of arachidonic acid (AA) and triggered the production of prostaglandin E2 (PGE2). An increased level of phosphorylated focal adhesion kinase (FAK) subsequently facilitated the reproliferation of SKOV3 cells, and VP-16-induced repopulation effects were partially reversed by the FAK inhibitor PF562271. Furthermore, the plasma AA-to-PGE2 ratio and tumoral FAK expression of ovarian cancer patients after chemotherapy were significantly lower than those before chemotherapy. Taken together, our results indicate that chemotherapy-induced apoptotic cancer cells can produce PGE2-enriched microenvironment through caspase 3-mediated AA metabolic pathway, which could lead to the abnormal activation of FAK and eventually accelerate the repopulation of SKOV3 cells. Our study provides novel insight into a mechanism that may be utilized to prevent ovarian cancer recurrence in response to chemotherapy.
Cancer is a daunting global problem confronting the world's population. The most frequent therapeutic approaches include surgery, chemotherapy, radiotherapy, and more recently immunotherapy. In the case of chemotherapy, patients ultimately develop resistance to both single and multiple chemotherapeutic agents, which can culminate in metastatic disease which is a major cause of patient death from solid tumors. Chemoresistance, a primary cause of treatment failure, is attributed to multiple factors including decreased drug accumulation, reduced drug-target interactions, increased populations of cancer stem cells, enhanced autophagy activity, and reduced apoptosis in cancer cells. Reprogramming tumor cells to undergo drug-induced apoptosis provides a promising and powerful strategy for treating resistant and recurrent neoplastic diseases. This can be achieved by downregulating dysregulated antiapoptotic factors or activation of proapoptotic factors in tumor cells. A major target of dysregulation in cancer cells that can occur during chemoresistance involves altered expression of Bcl-2 family members. Bcl-2 antiapoptotic molecules (Bcl-2, Bcl-xL, and Mcl-1) are frequently upregulated in acquired chemoresistant cancer cells, which block drug-induced apoptosis. We presently overview the potential role of Bcl-2 antiapoptotic proteins in the development of cancer chemoresistance and overview the clinical approaches that use Bcl-2 inhibitors to restore cell death in chemoresistant and recurrent tumors.
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
Background:
Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation. Subsequently, the synthesis of effective chemotherapeutic agents that can induce apoptosis in tumor cell has emerged as a significant approach in cancer drug discovery.
Methods:
The goal of this work is to develop a potential antitumor agent exerting significant inhibitory effects on cancer cell and low cytotoxicity, for which we focused on the structural features of 1,3,4-oxadiazoles as it a privileged scaffold in modern medicinal chemistry and have the ability to inhibit growth factors, enzymes and kinases potentially involved in the attainment of cellular immortality and carcinogenesis.
Result:
In vitro MTT screening assay showed the compound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e) showing the highest inhibitory effect against MCF-7 cancer cell with IC50 value 10.05 ± 1.08 µM while it is much safer and less toxic on normal cell line (HEK-293). The dose-dependent treatment of MCF-7 cells with 5e resulted in inhibition of cell migration in the wound healing assay. The flow-cytometry analysis showed the cells arrested in G0/G1 phase of the cell cycle. Compound 5e induced apoptosis of MCF-7 cells was characterized using DAPI staining and Annexin V-PE/7-AAD dual binding assay. Reduction of NBT by compound 5e showed a reduced generation of ROS. Western blotting studies showed high activation of apoptotic protein Caspase3 and decrease in expression of anti-apoptotic protein BCL-2.
Conclusion:
Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.
Glaucoma is the leading cause of irreversible blindness worldwide, affecting 64.3 million people. An estimated 60.5 million people are affected by primary open angle glaucoma globally, and this will increase to 111.8 million by 2040. The definition of glaucoma has evolved greatly over time. Although multiple risk factors such as ischemia, inflammation, myopia, race, age and low ocular perfusion pressure may play a role, intraocular pressure (IOP) is still the main risk factor we can easily identify and modify. Currently, both medical and surgical interventions aim to reduce IOP. Effective IOP reduction controls and prevents the progression in many cases of glaucoma. Although this multifactorial disease's true pathophysiology is difficult to elucidate, physiologic mediators including nitric oxide (NO) are being evaluated as novel ways to impact progression by both lowering IOP and improving optic nerve head perfusion. Latanoprostene bunod 0.024% is an emerging therapeutic agent that has shown promise in clinical trials. As a nitric oxide-donating prostaglandin F2-alpha receptor agonist, it has proven to effectively, and with good tolerability, reduce IOP in glaucoma and ocular hypertensive patients. Latanoprostene bunod capitalizes on NO's ability to modulate the conventional aqueous humor outflow system, directly improving outflow through the trabecular meshwork, Schlemm's canal and distal scleral vessels. Importantly, targeting the conventional outflow tissues with NO-donating drugs represents an opportunity to restore outflow function, which will most likely have a beneficial consequence of additional IOP-lowering effects with dampening of diurnal and other IOP fluctuations, the benefit of a healthy trabecular meshwork.
Cardiovascular disease is a compound name for clusters of disorders afflicting the heart and blood vessels; it is assuming an increasing role as a major cause of morbidity and mortality. Unhealthy practices such as smoking, high intake of saturated fat and cholesterol, diabetes and physical inactivity are predisposing factors. The risk factors cause alteration in vascular integrity, compromised membrane integrity, increase free radical generation and reduced endogenous antioxidant system resulting in oxidative stress. Substance with ability to maintain vascular integrity, prevent, or reduce radical formation are able to treat cardiovascular disease. Conventional drugs in use to this effect are with side effect and as alternative, medicinal plants are increasingly gaining acceptance from the public and medical professionals. Reports have shown that bioactive compounds in plants with antioxidant, anti-inflammatory, ability to protect vascular endothelium, prevent lipid oxidation, and augment endogenous antioxidant system are cardioprotective. Phenolics and flavonoids in medicinal plants have been widely reported to play these major roles. This study reviewed the role of bioactive compounds in medicinal plants using a wide range database search.
Introduction: Glutathione S – transferase (GST) is an important
enzyme in detoxification and helps in lowering oxidative stress.
It is speculated that this enzyme is induced under conditions of
oxidative stress as a protective mechanism.
Aim: To evaluate the status of Glutathione S–transferase in
Coronary artery disease patients with and without type 2
Diabetes mellitus.
Materials and Methods: The study was conducted in the
Department of Biotechnology, Swami Satyanand College of
Management and Technology in collaboration with Department
of Biochemistry, Govt Medical College Amritsar. A total of
133 diagnosed cases of Coronary Artery Disease (CAD) were
selected from the OPD and Medicine Ward of a private hospital,
Amritsar. CAD patients were segregated into two groups i.e.,
group-1 and group-2 on the basis if they had Type 2 Diabetes
mellitus or not. A total of 110 ages and sex matched healthy
individuals were taken as controls from the general population.
Written informed consent was obtained from all the subjects.
All the subjects were investigated for serum GST activity, Total
antioxidant status, plasma GSH levels, serum MDA and lipid
profile.
Results: Serum GST activity was significantly high (p
Silicon (Si) is the second most abundant element in soil, where its availability to plants can exhilarate to 10% of total dry weight of the plant. Si accumulation/transport occurs in the upward direction, and has been identified in several crop plants. Si application has been known to ameliorate plant growth and development during normal and stressful conditions over past two-decades. During abiotic (salinity, drought, thermal, and heavy metal etc) stress, one of the immediate responses by plant is the generation of reactive oxygen species (ROS), such as singlet oxygen (¹O2), superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH), which cause severe damage to the cell structure, organelles, and functions. To alleviate and repair this damage, plants have developed a complex antioxidant system to maintain homeostasis through non-enzymatic (carotenoids, tocopherols, ascorbate, and glutathione) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)]. To this end, the exogenous application of Si has been found to induce stress tolerance by regulating the generation of ROS, reducing electrolytic leakage, and malondialdehyde (MDA) contents, and immobilizing and reducing the uptake of toxic ions like Na, under stressful conditions. However, the interaction of Si and plant antioxidant enzyme system remains poorly understood, and further in-depth analyses at the transcriptomic level are needed to understand the mechanisms responsible for the Si-mediated regulation of stress responses.
The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase. These beneficial effects of CAP were reversed by treatment with the TRPV1 antagonists capsazepine and iodo-resiniferatoxin, indicating TRPV1 involvement. This study demonstrates that TRPV1 activation by CAP protects nigrostriatal DA neurons via inhibition of glial activation-mediated oxidative stress and neuroinflammation in the MPTP mouse model of PD. These results suggest that CAP and its analogs may be beneficial therapeutic agents for the treatment of PD and other neurodegenerative disorders that are associated with neuroinflammation and glial activation-derived oxidative damage.
The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To contend with such harmful compounds, living organisms have evolved antioxidant strategies. In this sense, the thiol-dependent antioxidant defense systems play a central role. In all cases, cysteine constitutes the major building block on which such systems are constructed, being present in redox substrates such as glutathione, thioredoxin, and trypanothione, as well as at the catalytic site of a variety of reductases and peroxidases. In some cases, the related selenocysteine was incorporated at selected proteins. In invertebrate parasites, antioxidant systems have evolved in a diversity of both substrates and enzymes, representing a potential area in the design of anti-parasite strategies. The present review focus on the organization of the thiol-based antioxidant systems in invertebrate parasites. Differences between these taxa and its final mammal host is stressed. An understanding of the antioxidant defense mechanisms in this kind of parasites, as well as their interactions with the specific host is crucial in the design of drugs targeting these organisms.
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis. Recent studies indicate new, alternative sources of oxidative stress in A-T, BS and NBS cells, including NADPH oxidase 4 (NOX4), oxidised low-density lipoprotein (ox-LDL) or Poly (ADP-ribose) polymerases (PARP). Mitochondrial abnormalities such as changes in the ultrastructure and function of mitochondria, excess mROS production as well as mitochondrial damage have also been reported in A-T, BS and NBS cells. A-T, BS and NBS cells are inextricably linked to high levels of reactive oxygen species (ROS), and thereby, chronic oxidative stress may be a major phenotypic hallmark in these diseases. Due to the presence of mitochondrial disturbances, A-T, BS and NBS may be considered mitochondrial diseases. Excess activity of antioxidant enzymes and an insufficient amount of low molecular weight antioxidants indicate new pharmacological strategies for patients suffering from the aforementioned diseases. However, at the current stage of research we are unable to ascertain if antioxidants and free radical scavengers can improve the condition or prolong the survival time of A-T, BS and NBS patients. Therefore, it is necessary to conduct experimental studies in a human model.
In this review article we examine the role of glutathione reductase in the regulation, modulation and maintenance of cellular redox homoeostasis. Glutathione reductase is responsible for maintaining the supply of reduced glutathione; one of the most abundant reducing thiols in the majority of cells. In its reduced form, glutathione plays key roles in the cellular control of reactive oxygen species. Reactive oxygen species act as intracellular and extracellular signalling molecules and complex cross talk between levels of reactive oxygen species, levels of oxidised and reduced glutathione and other thiols, and antioxidant enzymes such as glutathione reductase determine the most suitable conditions for redox control within a cell or for activation of programmed cell death. Additionally, we discuss the translation and expression of glutathione reductase in a number of organisms including yeast and humans. In yeast and human cells, a single gene expresses more than one form of glutathione reductase, destined for residence in the cytoplasm or for translocation to different organelles; in plants, however, two genes encoding this protein have been described. In general, insects and kinetoplastids (a group of protozoa, including Plasmodia and Trypanosoma) do not express glutathione reductase or glutathione biosynthetic enzymes. Instead, they express either the thioredoxin system or the trypanothione system. The thioredoxin system is also present in organisms that have the glutathione system and there may be overlapping functions with cross-talk between the two systems. Finally we evaluate therapeutic targets to overcome oxidative stress associated cellular disorders.
Leaf, seed, and tuber explants of C. latifolia were inoculated on MS medium supplemented with various concentrations of BAP and IBA, alone or in combinations, to achieve in vitro plant regeneration. Subsequently, antioxidant and antibacterial activities were determined from in vitro and in vivo plant developed. No response was observed from seed culture on MS media with various concentrations of PGRs. The highest percentage of callus was observed on tuber explants (94%) and leaf explants (89%) when cultured on MS media supplemented with IBA in combination with BAP. A maximum of 88% shoots per tuber explant, with a mean number of shoots (
8.8
±
1.0
), were obtained on MS medium supplemented with combinations of BAP and IBA (2.5 mg L−1). The best root induction (92%) and mean number (
7.6
±
0.5
) from tuber explants were recorded on 2.5 mg L−1 IBA alone supplemented to MS medium. The higher antioxidant content (80%) was observed from in vivo tuber. However, tuber part from the intact plant showed higher inhibition zone in antibacterial activity compared to other in vitro and in vivo tested parts.
Hepatocellular carcinoma is one of the most common lethal diseases worldwide and there is no effective treatment till date. Natural products derived from the plants play an important role in chemoprevention and act as therapeutic antitumor agents. Licorice is a plant that has been used in food and medicine for the treatment of various diseases. 18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid obtained from the roots of licorice plant, is reported to possess various pharmacological properties such as antitumor and antiinflammatory activities. The present study was designed to elucidate the chemopreventive effect of 18β-GA through antiinflammation, antiproliferation, and induction of apoptosis in human hepatoma cell line HepG2. 18β-GA significantly inhibits the proliferation of HepG2 cell without affecting the normal liver cell line (Chang's). In the present study, 18β-GA increased the formation of reactive oxygen species, nitric oxide production, and loss of mitochondrial membrane potential, suggesting the involvement of 18β-GA in apoptosis which was also confirmed by assessing the markers involved in apoptosis like caspase-3, caspase-9, Bax:Bcl-2 ratio, and cleaved PARP. 18β-GA also downregulated the expression of inflammatory proteins such as NF-κB, iNOS, and COX-2. Keeping these data into consideration, our results suggest that 18β-GA may be used as a chemopreventive agent in liver cancer.
The aim of this study was to gain more complete information about the relationships between some endogenous antioxidants and the malondialdehyde (MDA) as a marker of lipid peroxidation, during D-galactose induced senescence. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and the concentrations of uric acid (UA) in plasma and MDA in erythrocyte's hemolysate, were determined in 15 D-galactose (D-gal), treated rats and compared with 15 placebo. The activity of the erythrocyte's CAT was found significantly increased due to the senescence. The ratio of the activities of antioxidant enzymes R=SOD/(GPx+CAT) was significantly decreased due to the senescence and negatively correlated with the MDA (ρ=–0.524, p=0.045). The antioxidant enzymes SOD and GPx negatively correlated with the MDA, while CAT displayed no correlation. Further, the UA positively correlated with the ratio of activities of the antioxidant enzymes R=SOD/(GPx+CAT), (ρ=0.564, p=0.029 for senescent rats). Obtained results may contribute to better understanding of the process of D-gal induced senescence in the erythrocytes.
Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natual flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25,50 and 100mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF- α concentrations. Moreover, naringin inhibited NF- κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease.
Plants have been one of the important sources of medicine even since the-dawn of human civilization. Curcumin has been found to possess tremendous therapeutic potency as antiinflammatory, antioxidant and antimicrobial agent. The present study was designed to examine possible potential therapeutic and protective effect of curcumin from oxidative stress and on total antioxidant capacity in liver damage. The study was conducted using H2O2 as inducing agent of oxidative stress in vivo. Rats were randomly divided into five groups, where n = 20 for each group. Group 1 (G1) rats served as control group. Group 2 (G2) rats subjected to experimentally induced oxidative stress by the ad libitum supply of drinking water containing 0.5% H2O2(v/v) was prepared daily over entire 60 days. Group 3 (G3) rats received H2O2 for sixty days followed by giving 200 mg kg(-1) of curcumin for 30 days. Group 4 (G4) was simultaneously given curcumin (200 mg kg(-1)) for 15 days then followed by receiving H2O2 with curcumin for sixty days. Group 5 (G5) rats was received H2O2 for sixty days followed by giving 200 mg kg(-1) of N-acetyl 1-cystine as standard drug for 30 days. Levels of marker enzymes (ALT, AST and ALP), uric acid, Total Protein (TP) and tumor necrosis factor (α-TNF) were assessed in serum for all studied groups. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguinosine, Total Antioxidant Capacity (TAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) were assayed in liver homogenates for all studied groups. The results revealed significant increase (p < 0.05) in levels of ALT, AST, ALP, uric acid and α-TNF while there are significant decrease (p < 0.05) in levels of TP in G2 comparing to G1. Also there are significant differences (p < 0.05) between G3 and G4 comparing to G2 and between G3, G4 and G5 which curcumin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation. The results also revealed a significant increase (p < 0.05) in levels of MDA and 8-H-2-deoxy guinosine while there was significant reduction (p < 0.05) in TAC, GSH, SOD and catalase in G2 comparing to G1. Also there are significant differences (p < 0.05) between G3 and G4 comparing to G2 and between G3, G4 and G5. The conclusion could be drown from this study that the ability of curcumin as therapeutic agent and hepatoprotective against liver damage from oxidative damage and on TAC more than N-acetyl 1-cystine related to its antioxidant and free radical scavenger activity.
Free radicals are one of the frequent products of normal cellular metabolism. Disparity of metabolism and excessive generation of free radicals predisposes to disorders like Parkinson's disease, Alzheimer's disease, and aging phenomenon. Curculigo orchioides Gaertn. is known for "adaptogen" and "aphrodisiac" activity and has been proved for antiasthmatic, estrogenic, antiosteoporotic activity along with protection from cisplatin-induced cell damage. C. orchioides was powdered and subjected to soxhlet extraction using methanol. Phytochemical studies and estimation of polyphenols and flavonoids was performed. Acute toxicity studies were performed by Organization for Economic Cooperation and Development OECD guidelines. Animals were treated with cyclophosphamide to induce neurotoxicity. Curculigo orchioides was powdered and subjected to soxhlet extraction using methanol. Catalase, superoxide dismutase, glutathione peroxidase, and lipid peroxidation were estimated by reported methods. C. orchioides (400 mg/kg) significantly promoted restoration of catalase (P < 0.005), superoxide dismutase (P < 0.005), and glutathion (P < 0.05) levels. Similarly, a very significant decrease (P < 0.005) in the levels of malondialdehyde was observed. In all cases as mentioned previously, C. orchioides at dose 200 mg/kg promoted significant (P < 0.05) restoration of enzyme levels. C. orchioides (Kali Musli) is rich source of phytochemicals like flavonoids and polyphenols. Flavonoids and polyphenols are reputed to demonstrate neuroprotective effect. These phytochemicals in the present study might be responsible to demonstrate neuroprotective effect.
Cyclophosphamide (CTX) is a synthetic antineoplastic drug with severe and life-threatening side effects. Studies in search of protective agents, preferably natural products, that can alleviate these side effects are valuable because they can contribute to improve current chemotherapeutic treatment strategies. Curculigo orchioides Gaertn (family Hypoxidaceae) is well known for its medicinal use in the Indian Ayurvedic system of medicine, and various studies have been reported that proved its immunomodulatory and anti-inflammatory properties. In this study, the tumor reduction capacity of CTX in combination with C orchioides methanolic extract was studied using Dalton's lymphoma ascites-induced solid tumor models. Effect of C orchioides on the reversal of the damage induced by CTX administration (intraperitoneally) was also determined in this study. For this, solid tumor volume, serum cytokine levels, hematolological parameters, intestinal histopathology, and serum and tissue biochemical parameters (Glutathione [GSH], alkaline phosphatase [ALP], glutamate pyruvate transaminase [GPT], lipid peroxidation [LPO]) were analyzed. Immune suppression and increased serum proinflammatory cytokine levels caused by CTX administration (25 mg/kg body weight) were reversed by C orchioides (20 mg/kg body weight). The alcoholic extract enhanced the tumor reduction capacity of CTX and reduced GPT and ALP levels in liver and serum, which were elevated by CTX administration. The LPO level was also lower in the CTX-administered animals when treated with the C orchioides extract. In conclusion, the plant extract when administered in combination with CTX, can result in enhanced anticancer properties; it also ameliorates the toxic side effects of CTX.
© The Author(s) 2015.
In the past few years, there has been a renewed interest in studying a wide variety of food products that show beneficial effects on human health. Capsicum is an important agricultural crop, not only because its economic importance, but also for the nutritional values of its pods, mainly due to the fact that they are an excellent source of antioxidant compounds, and also of specific constituents such as the pungent capsaicinoids localized in the placental tissue. This current study was designed to evaluate the antioxidant capacity and total phenolic contents from fruits tissues of two Capsicum chinense accessions, namely, Chak k'an-iik (orange) and MR8H (red), at contrasting maturation stages. Results showed that red immature placental tissue, with a Trolox equivalent antioxidant capacity (TEAC) value of 55.59 μ mols TE g(-1) FW, exhibited the strongest total antioxidant capacity using both the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the CUPRAC methods. Placental tissue also had the highest total phenolic content (27 g GAE 100 g(-1) FW). The antioxidant capacity of Capsicum was directly related to the total amount of phenolic compounds detected. In particular, placentas had high levels of capsaicinoids, which might be the principal responsible for their strong antioxidant activities.
Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These "biological vectors" can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.
Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.
Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species, as well as to regulate redox-sensitive signaling pathways. General protocols are described to measure the antioxidant enzyme activity of superoxide dismutase (SOD), catalase and glutathione peroxidase. The SODs convert superoxide radical into hydrogen peroxide and molecular oxygen, whereas the catalase and peroxidases convert hydrogen peroxide into water. In this way, two toxic species, superoxide radical and hydrogen peroxide, are converted to the harmless product water. Western blots, activity gels and activity assays are various methods used to determine protein and activity in both cells and tissue depending on the amount of protein required for each assay. Other techniques including immunohistochemistry and immunogold can further evaluate the levels of the various antioxidant enzymes in tissues and cells. In general, these assays require 24-48 h to complete.
Piperine (PP), an alkaloid from black and long peppers (Piper nigrum Linn &Piper longum Linn), exhibits antitumor activities in vitro and in vivo. We investigated the ability of piperine (PP) to reverse the drug resistance of human cervical cancer cells. In our study, the cervica cancer cells resistant to mitomycin-C (MMC) treatment were used. We found the growth inhibitory effects of piperine on human cervical cancer cell, which were resistant to MMC. Piperine and MMC co-treatment resulted in a dose-dependent suppression of the cell proliferation. Decreasing of phosphorylated-signal transducer and activator of transcription (p-STAT3) was linked to the suppression of p65 by PP and MMC combinational treatment. Additionally, the presence of PP potentiated the effects of MMC on apoptosis induction in cervical cancer cells with drug resistance, which was dependent on Bcl-2 inhibition. The pro-apoptotic proteins of Bax and Bid were up-regulated, accompanied with Caspase cleavage. Moreover, in mice xenograft models, the combined therapy inhibited tumor growth compared to the PP or MMC mono-therapy group. Our data indicated a novel therapeutic strategy of PP to potentiate MMC-induced anti-tumor effect on cervical cancer cells with drug resistance through blocking p-STAT3/p65 and Bcl-2 activation.
Plant-derived substances (phytochemicals) are well recognized as sources of pharmacologically potent drugs in the treatment of several oxidative stress related disorders. Our study aims to evaluate the antioxidant and apoptotic effects of Glycyrrhiza glabra L. in both cell free and cell culture system. Plant fractions have been prepared with hexane, chloroform, ethyl acetate, methanol and water and their antioxidant properties are reviewed. Potent antioxidant activity has been well established in both in vitro and in silico studies which is believed to be responsible for the anticancerous nature of the plant. Results obtained indicate that methanol fraction of G. glabra L. exhibited maximum scavenging activity against DPPH and nitric oxide free radicals comparable to standard antioxidant L-AA. Administration of methanol fraction also considerably reduced the malondialdehyde produced due to lipid peroxidation in mammalian liver tissues. Moreover, the levels of antioxidant enzymes SOD, CAT, GST, GPx and GR in the oxidative stress induced tissues were refurbished significantly after treatment with plant’s methanol fraction. Moreover, methanol fraction was found to be nontoxic to normal human cell line whereas it inhibited cancer cells HeLa and HepG2 considerably. Apoptosis was established by DAPI fluorescent staining and western blot analysis of pro apoptotic protein caspase-8, caspase-3 and anti-apoptotic protein Bcl-2.There is an up regulation in the levels of pro apoptotic caspase-8 and caspase-3 and down regulation of anti-apoptotic Bcl-2. Furthermore, GC–MS analysis of the methanol fraction revealed the presence of many compounds. In silico experiments using Autodock 4.2 tools showed strong affinity of plant compounds towards antioxidant enzymes (proteins) thus validating with the conclusions of antioxidant enzyme assays and establishing a role in cancer pathogenesis.