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International Journal of Molecular... Mar 2024C19 steroids and C22 steroids are vital intermediates for the synthesis of steroid drugs. Compared with C19 steroids, C22 steroids are more suitable for synthesizing...
C19 steroids and C22 steroids are vital intermediates for the synthesis of steroid drugs. Compared with C19 steroids, C22 steroids are more suitable for synthesizing progesterone and adrenocortical hormones, albeit less developed. 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one(9-OHBA), due to its substituents at positions C-9 and C-22, is a beneficial and innovative steroid derivative for synthesizing corticosteroids. We focused on the C22 pathway in ATCC 35855, aiming to develop a productive strain that produces 9-OHBA. We used a mutant strain, MFΔ, that knocked out from ATCC 35855 named MFKD in this study as the original strain. Hsd4A and FadA5 are key enzymes in controlling the C19 metabolic pathway of steroids in ATCC 35855. After knocking out , MFKDΔ accumulated 81.47% 9-OHBA compared with 4.13% 9-OHBA in the strain MFKD. The double mutant MFKDΔΔ further improved the selectivity of 9-OHBA to 95.13%, and 9α-hydroxy-4-androstenedione (9-OHAD) decreased to 0.90% from 4.19%. In the end, we obtained 6.81 g/L 9-OHBA from 10 g/L phytosterols with a molar yield of 80.33%, which showed the best performance compared with formerly reported strains.
Topics: Mycobacterium fortuitum; Androstenedione; Molar; Phytosterols; Progesterone
PubMed: 38612391
DOI: 10.3390/ijms25073579 -
Foods (Basel, Switzerland) Apr 2024With the increasing impacts of climate change, establishing more sustainable and robust plants such as desert dates () seems to be necessary. Known for its resilience in...
With the increasing impacts of climate change, establishing more sustainable and robust plants such as desert dates () seems to be necessary. Known for its resilience in arid conditions, this tree has the potential to become a more important food source, particularly for its potential to yield edible oil. This study characterized kernel oil (BKO) as a promising oil source in arid regions, studying the influence of geographical origin and environmental factors. Moroccan and Sudanese BKO samples were analyzed and compared with Mauritanian BKO. In the fatty acid profile, unsaturated fatty acids constituted over 70% of the BKO profile, with a predominance of linoleic acid (Li), oleic acid (Ol), palmitic acid (Pa), and stearic acid (St). Consequently, the predominant triacylglycerols were PaLiLi, PaLiOl, LiLiOl, OlLiOl, and StLiOl. α-Tocopherol dominated the tocochromanol composition (324 to 607 mg/kg), followed by γ-tocopherol (120 to 226 mg/kg), constituting 90% of the total tocochromanols. The total phytosterol content in BKO ranged from 871 to 2218 mg/kg oil, with β-sitosterol dominating (58% to 74%). Principal Component Analysis revealed that the geographical origin significantly influences BKO composition, emphasizing environmental factors, particularly water deficit and/or temperatures. Notably, Moroccan BKO collected from an area characterized by high aridity and relatively low winter temperatures, showcased a unique profile in fatty acid, phytosterols, and tocochromanols. The valorization of BKO presents an opportunity for local agricultural development in arid regions and a role model for plant development and agricultural practices in other parts of the world.
PubMed: 38611439
DOI: 10.3390/foods13071135 -
Foods (Basel, Switzerland) Mar 2024The increasing population, food demand, waste management concerns, and the search for sustainable alternatives to plastic polymers have led researchers to explore the...
The increasing population, food demand, waste management concerns, and the search for sustainable alternatives to plastic polymers have led researchers to explore the potential of waste materials. This study focused on a waste of pine nut processing referred to in this paper as pine nut skin. For the first time, its nutritional profile, potential bioactive peptide, contaminants, and morphological structure were assessed. Pine nut skin was composed mainly of carbohydrates (56.2%) and fiber (27.5%). The fat (9.8%) was about 45%, 35%, and 20% saturated, monounsaturated, and polyunsaturated fatty acid, respectively, and Omega-9,-6, and -3 were detected. Notably, oleic acid, known for its health benefits, was found in significant quantities, resembling its presence in pine nut oil. The presence of bioactive compounds such as eicosapentaenoic acid (EPA) and phytosterols further adds to its nutritional value. Some essential elements were reported, whereas most of the contaminants such as heavy metals, polycyclic aromatic hydrocarbons, rare earth elements, and pesticides were below the limit of quantification. Furthermore, the in silico analysis showed the occurrence of potential precursor peptides of bioactive compounds, indicating health-promoting attributes. Lastly, the morphological structural characterization of the pine nut skin was followed by Fourier Transform Infrared and solid-state NMR spectroscopy to identify the major components, such as lignin, cellulose, and hemicellulose. The thermostability of the pine nut skin was monitored via thermogravimetric analysis, and the surface of the integument was analyzed via scanning electron microscopy and volumetric nitrogen adsorption. This information provides a more comprehensive view of the potential uses of pine nut skin as a filler material for biocomposite materials. A full characterization of the by-products of the food chain is essential for their more appropriate reuse.
PubMed: 38611351
DOI: 10.3390/foods13071044 -
Microbial Cell Factories Apr 2024Pregnenolone and progesterone are the life-important steroid hormones regulating essential vital functions in mammals, and widely used in different fields of medicine....
BACKGROUND
Pregnenolone and progesterone are the life-important steroid hormones regulating essential vital functions in mammals, and widely used in different fields of medicine. Microbiological production of these compounds from sterols is based on the use of recombinant strains expressing the enzyme system cholesterol hydroxylase/C20-C22 lyase (CH/L) of mammalian steroidogenesis. However, the efficiency of the known recombinant strains is still low. New recombinant strains and combination approaches are now needed to produce these steroid hormones.
RESULTS
Based on Mycolicibacterium smegmatis, a recombinant strain was created that expresses the steroidogenesis system (CYP11A1, adrenodoxin reductase, adrenodoxin) of the bovine adrenal cortex. The recombinant strain transformed cholesterol and phytosterol to form progesterone among the metabolites. When 3-methoxymethyl ethers of sterols were applied as bioconversion substrates, the corresponding 3-ethers of pregnenolone and dehydroepiandrosterone (DHEA) were identified as major metabolites. Under optimized conditions, the recombinant strain produced 85.2 ± 4.7 mol % 3-methoxymethyl-pregnenolone within 48 h, while production of 3-substituted DHEA was not detected. After the 3-methoxymethyl function was deprotected by acid hydrolysis, crystalline pregnenolone was isolated in high purity (over 98%, w/w). The structures of steroids were confirmed using TLC, HPLC, MS and H- and C-NMR analyses.
CONCLUSION
The use of mycolicybacteria as a microbial platform for the expression of systems at the initial stage of mammalian steroidogenesis ensures the production of valuable steroid hormones-progesterone and pregnenolone from cholesterol. Selective production of pregnenolone from cholesterol is ensured by the use of 3-substituted cholesterol as a substrate and optimization of the conditions for its bioconversion. The results open the prospects for the generation of the new microbial biocatalysts capable of effectively producing value-added steroid hormones.
Topics: Cattle; Animals; Progesterone; Pregnenolone; Sterols; Steroids; Cholesterol; Cholesterol Side-Chain Cleavage Enzyme; Phytosterols; Mammals; Ethers
PubMed: 38594656
DOI: 10.1186/s12934-024-02385-2 -
Planta Medica May 2024Cancer is one of the biggest health concerns with a complex pathophysiology. Currently, available chemotherapeutic drugs are showing deleterious side effects, and tumors... (Review)
Review
Cancer is one of the biggest health concerns with a complex pathophysiology. Currently, available chemotherapeutic drugs are showing deleterious side effects, and tumors often show resistance to treatment. Hence, extensive research is required to develop new treatment strategies to fight against cancer. Natural resources from plants are at the forefront of hunting novel drugs to treat various types of cancers. Withaferin A (WA) is a naturally occurring withanolide, a biologically active component obtained from the plant Ashwagandha. Various and oncological studies have reported that Withaferin A (WA) has shown protection from cancer. WA shows its activity by inhibiting the growth and proliferation of malignant cells, apoptosis, and inhibiting angiogenesis, metastasis, and cancer stem cells (CSCs). In addition, WA also showed chemo- and radio-sensitizing properties. Besides the beneficiary pharmacological activities of WA, a few aspects like pharmacokinetic properties, safety, and toxicity studies are still lacking, hindering this potent natural product from entering clinical development. In this review, we have summarized the various pharmacological mechanisms shown by WA in and cancer studies and the challenges that must be overcome for this potential natural product's clinical translation to be effective.
Topics: Withanolides; Humans; Neoplasms; Animals; Biological Products; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Proliferation
PubMed: 38588695
DOI: 10.1055/a-2289-9600 -
Aging Apr 2024Stigmasterol is a common dietary phytosterol with high nutritional value and physiological activity. In this study, we evaluated the effects of stigmasterol on...
Stigmasterol is a common dietary phytosterol with high nutritional value and physiological activity. In this study, we evaluated the effects of stigmasterol on inflammatory cytokines and the TGF-β1/Smad2 and IL-17A signaling pathway in an ovalbumin (OVA)-induced asthma mouse model. Stigmasterol treatment improved airway remodeling. In addition, it significantly attenuated the symptoms of asthma attacks, reduced the number of macrophages, lymphocytes, neutrophils, and eosinophils in BALF and inflammatory cytokines, including IL-1β, IL-5, IL-6, and IL-13. It further decreased the level of IL-17A in BALF, serum and spleen. Spleen single-cell suspension analysis via flow cytometry showed that IL-17A level was consistent with the results obtained in BALF, serum and spleen. Stigmasterol decreased the protein expression levels of TGF-β, p-Smad2 and IL-17A in the spleen, by increasing the protein expression level of IL-10. After 24 h of co-culture of TGF-β, IL-6 and stigmasterol, the level of IL-17 in CD4 T cell supernatant was lower relative to levels in the group without stigmasterol. Meanwhile, stigmasterol treatment attenuated the expression level of TGF- β, p-Smad2 and IL-17A proteins in CD4 T cells and enhanced the expression levels of IL-10 protein. These data suggested that stigmasterol inhibited the TGF-β1/Smad2 and IL-17A signaling pathway to achieve anti-asthmatic effects in the OVA-induced asthma mouse model. Collectively, the results of this study are that stigmasterol has achieved preliminary efficacy in the non-clinical laboratory, further studies are needed to consider the clinical application of stigmasterol.
Topics: Animals; Asthma; Smad2 Protein; Mice; Transforming Growth Factor beta1; Signal Transduction; Ovalbumin; Interleukin-17; Stigmasterol; Disease Models, Animal; Mice, Inbred BALB C; Female; Airway Remodeling; Inflammation
PubMed: 38579176
DOI: 10.18632/aging.205716 -
Frontiers in Pharmacology 2024Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense... (Review)
Review
Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. L. (), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of . The keyword "" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in , including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from . This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of . This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.
PubMed: 38576489
DOI: 10.3389/fphar.2024.1322083 -
CNS Neuroscience & Therapeutics Apr 2024This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain.
AIMS
This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain.
METHODS
Related mechanisms were investigated by DRG single-cell sequencing analysis and the use of specific inhibitors in cellular experiments. In animal experiments, 32 male Sprague-Dawley rats were randomly divided into the sham operation group, CCI group, ibuprofen group, and stigmasterol group. We performed behavioral tests, ELISA, H&E staining and immunohistochemistry, and western blotting.
RESULTS
Cell communication analysis by single-cell sequencing reveals that after peripheral nerve injury, Schwann cells secrete IL-34 to act on CSF1R in macrophages. After peripheral nerve injury, the mRNA expression levels of CSF1R pathway and NLRP3 inflammasome in macrophages were increased in DRG. In vitro studies demonstrated that stigmasterol can reduce the secretion of IL-34 in LPS-induced RSC96 Schwann cells; stigmasterol treatment of LPS-induced Schwann cell-conditioned medium (L-S-CM) does not induce the proliferation and migration of RAW264.7 macrophages; L-S-CM reduces CSF1R signaling pathway (CSF1R, P38MAPK, and NFκB) activation, NLRP3 inflammasome activation, and ROS production. In vivo experiments have verified that stigmasterol can reduce thermal and cold hyperalgesia in rat chronic compressive nerve injury (CCI) model; stigmasterol can reduce IL-1β, IL-6, TNF-α, CCL2, SP, and PGE2 in serum of CCI rats; immunohistochemistry and western blot confirmed that stigmasterol can reduce the levels of IL-34/CSF1R signaling pathway and NLRP3 inflammasome in DRG of CCI rats.
CONCLUSION
Stigmasterol alleviates neuropathic pain by reducing Schwann cell-macrophage cascade in DRG by modulating IL-34/CSF1R axis.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; NLR Family, Pyrin Domain-Containing 3 Protein; Stigmasterol; Inflammasomes; Peripheral Nerve Injuries; Lipopolysaccharides; Neuralgia; Hyperalgesia; Interleukins; Macrophages; Schwann Cells
PubMed: 38572785
DOI: 10.1111/cns.14657 -
Cureus Mar 2024Background species are perennial shrubs and flowering plants belonging to the family . The leaf and flower parts of ()and () aimed at isolating their active...
Background species are perennial shrubs and flowering plants belonging to the family . The leaf and flower parts of ()and () aimed at isolating their active fractions. The present study was to determine in vitro antitumor activity against malignant melanoma cell lines for phytosome formulation. Materials and methods Two species, (red flowers and leaves) and (white flowers and leaves), were selected, and this study focused on determining the active fraction by comparing the in vitro antimicrobial and antioxidant potentials of petroleum ether, chloroform, ethyl acetate, and hydroalcoholic (ethanol:water, 70:30 v/v) extracts. The identified potent extract was subjected to in vitro anticancer activity in malignant melanoma cell lines. Results A phytochemical study revealed phytosterols, flavonoids, proteins, amino acids, alkaloids, carbohydrates, phenols, tannins, and diterpenes. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to evaluate the antioxidant effect of leaf and flower extracts. In the DPPH assay, flower hydroalcoholic extract (ICFHA) had an IC value of 248.99 µg/mL, and leaf hydroalcoholic extract (ICLHA) had an IC value of 268.87 µg/mL. These two extracts had a lower value with a higher antioxidant effect. In the total antioxidant assay, leaf ethyl acetate extract (ICLEA) and leaf chloroform extract (ICLCE) have 77.4 ± 0.05 and 68.9 ± 0.03 mg of ascorbic acid equivalent per gm of extract, respectively. These two extracts exhibited a high antioxidant effect. The antimicrobial potential was evaluated using selected bacterial and fungal strains using the agar-well diffusion method. Petroleum ether and chloroform extracts of and leaves and flowers did not possess antimicrobial activity with any of the bacterial or fungal strains. An ethyl acetate extract and a hydroalcoholic extract of leaves and flowers showed antimicrobial activity against , , and . An ethyl acetate extract of flower and a hydroalcoholic extract of leaf showed a significant zone of inhibition when compared with standard chloramphenicol for all three selected strains, which may be due to the presence of active phytoconstituents. ICLHA showed a MIC of ≤300 µg/mL for and and ≤400 µg/mL for microbial strains. The high total flavonoid content was reported in ICLEA at 771.31 µg/mL and in flower ethyl acetate extract (ICFEA) at 694.69 µg/mL. High-performance thin layer chromatography (HPTLC) analysis showed a high quercetin (QCE) content in the ICLEA extract. To prove the in vitro skin anticancer activity, an MTT assay was performed for the ICLEA extract in a malignant melanoma cell line, and the IC50 value was reported as 7.96 µg/mL. Conclusion leaf ethyl acetate extract revealed a significant total flavonoid content in analysis through the aluminum chloride method, and the presence of a high QCE content was confirmed by HPTLC analysis. The in vitro skin anticancer activity of ICLEA was confirmed by the MTT assay; therefore, it was concluded that the ICLEA extract was a potent fraction and was selected to develop a phytosome.
PubMed: 38562312
DOI: 10.7759/cureus.55396 -
PeerJ 2024Maize production and productivity are affected by drought stress in tropical and subtropical ecologies, as the majority of the area under maize cultivation in these...
Maize production and productivity are affected by drought stress in tropical and subtropical ecologies, as the majority of the area under maize cultivation in these ecologies is rain-fed. The present investigation was conducted to study the physiological and biochemical effects of 24-Epibrassinolide (EBR) as a plant hormone on drought tolerance in maize. Two maize hybrids, Vivek hybrid 9 and Bio 9637, were grown under three different conditions: (i) irrigated, (ii) drought, and (iii) drought+EBR. A total of 2 weeks before the anthesis, irrigation was discontinued to produce a drought-like condition. In the drought+EBR treatment group, irrigation was also stopped, and in addition, EBR was applied as a foliar spray on the same day in the drought plots. It was observed that drought had a major influence on the photosynthesis rate, membrane stability index, leaf area index, relative water content, and leaf water potential; this effect was more pronounced in Bio 9637. Conversely, the activities of antioxidant enzymes such as catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD) increased in both hybrids under drought conditions. Specifically, Vivek hybrid 9 showed 74% higher CAT activity under drought conditions as compared to the control. Additionally, EBR application further enhanced the activity of this enzyme by 23% compared to plants under drought conditions. Both hybrids experienced a significant reduction in plant girth due to drought stress. However, it was found that exogenously applying EBR reduced the detrimental effects of drought stress on the plant, and this effect was more pronounced in Bio 9637. In fact, Bio 9637 treated with EBR showed an 86% increase in proline content and a 70% increase in glycine betaine content compared to untreated plants under drought conditions. Taken together, our results suggested EBR enhanced tolerance to drought in maize hybrids. Hence, pre-anthesis foliar application of EBR might partly overcome the adverse effects of flowering stage drought in maize.
Topics: Zea mays; Stress, Physiological; Droughts; Antioxidants; Water; Steroids, Heterocyclic; Brassinosteroids
PubMed: 38560461
DOI: 10.7717/peerj.17190