The Analgesic and Anti-inflammatory Effects of Partially Purified Polysaccharide Fractions of Cell-free Medium and Biomass of Spirulina platensis PCST5.

Background: Spirulina is a cyanobacteria species containing various bioactive compounds. Spirulina is a known source of nutrients in some traditional diets. Different activities have been reported for various extracts of S. platensis. Objectives: In this study, the polysaccharide content of culture media and biomass extract of one species of Spirulina was partially purified, and its analgesic and anti-inflammatory effects were evaluated. Methods: Spirulina platensis PCST5 was cultured in a sterile Zarouk medium at 27°C and 16/8h of light/ dark exposure cycle for 25 days. Then, the polysaccharide content of biomass and cell-free culture medium samples (BPSs and CFPSs, respectively) was partially purified. The analgesic and anti-inflammatory effects were evaluated using animal models. Results: 16S rRNA gene analysis confirmed that the organism was genetically similar to Spirulina platensis. The CFPSs (30 and 100 mg/kg) and BPSs (30 mg/kg) significantly reduced pain-related behaviors in rats. Similarly, all samples could significantly reduce carrageenan-induced paw inflammation volume compared with the control group. Our results suggest Spirulina's polysaccharide fractions (CFPSs and BPSs) had significant analgesic and anti-inflammatory effects. Conclusions: Since Spirulina is a readily available source of bioactive compounds, finding such potent anti-inflammatory and anti-nociceptive compounds can provide promising leads for novel drug development.

Culture Optimization to Produce High Yields of Mycosporine-Like Amino Acids by Fischerella sp. F5.

Fischerella sp. is a valuable source of active metabolites, including UV-protecting compounds, among which mycosporin-like amino acids (MAAs) can be mentioned. Mycosporine-like amino acids are attractive secondary metabolites of a wide range of microorganisms, including microalgae and cyanobacteria. Enhanced production of MAAs has been studied in different sources. This study aimed to optimize the phosphate and nitrate concentrations of the culture medium on BG11 to maximize MAAs production from Fischerella sp. F5, using response surface methodology. The extraction process from the cultures, grown in adjusted conditions, was also optimized. The results confirmed that increasing both, nitrate and phosphate concentration, in the culture medium had a positive effect on the MAAs production by Fischerella sp. F5. While, optimization of the extraction process was not led to a highly accurate predictive model; temperature, sonication time, methanol ratio, and solvent/biomass ratio exhibited significant effects on the final MAAs' concentration in partially purified extracts. In general, more optimization cultures studies need to complete these findings in reference to MAAs production and extraction from Fischerella sp. F5, for commercial-scale applications.

A Study on the Effect of Nitrate and Phosphate Concentrations on the Production of Mycosporine-Like Amino Acids by Chlorella Vulgaris.

Background: Cyanobacteria can produce compounds absorbing ultraviolet irradiation. Mycosporine like amino acids (MAAs) are some of these important metabolites, which can be potentially considered as a sunscreen agent in the pharmaceutical and cosmetic industry. Different factors have been reported that can affect the biosynthesis of MAA. Objective: In this study, the influence of different concentrations of phosphate and nitrate under different environmental conditions on MAA production by Chlorella vulgaris was investigated using an experimental design method, in order to enhance MAAs production in this specious. Materials and Methods: A 23 full factorial design (FFD) using Design-Expert v7.0.0 software was used to optimize simultaneously all the three factors of nitrate and phosphate concentration and condition of incubation environment on the MAA production by this species of C. vulgaris. Two milliliter of organism stock were grown in 200 mL BG11 medium and after 21 days, the biomasses of all samples were separated. Then, the MAA was extracted from dried biomass using methanol extraction. The extracts were analyzed by reverse-phase high performance liquid chromatography (RP-HPLC). After complete analysis, four samples were then cultured at the optimized conditions and analyzed by liquid chromatohraphy coupled to mass spectrometry (LC/MS). Results: The results showed that this microalga could produce compounds with λmax of 330 nm and a retention time of about 2 min. According to the central composite analysis, phosphate at 0.51 g.L-1 and nitrate at 2.5 g.L-1 can be considered as the optimum concentrations, resulting to the preferable conditions concerning the culture in germinator. Based on LC/MSS analysis, the major compound had a m/z of 332 at the optimum condition. Conclusion: Thus, this species is expected to have the capability of MAA production (maybe Shinorine) or one of its glycosylated derivatives.

Efficacy of a multiple-indication antiviral herbal drug (Saliravira®) for COVID-19 outpatients: A pre-clinical and randomized clinical trial study.

BACKGROUND: The scientific researches on COVID-19 pandemic topics are headed to an explosion of scientific literature. Despite these global efforts, the efficient treatment of patients is an in-progress challenge. Based on a meta-study of published shreds of evidence about compounds and their botanic sources in the last six decades, a novel multiple-indication herbal compound (Saliravira®) has been developed. Based on the antiviral, anti-inflammatory, and immune-enhancing properties of its ingredients, we hypothesized that Saliravira® has the potential to act as an antiviral agent, accelerate treatment, and reduce undesirable effects of COVID-19. METHODS: In this randomized, controlled, open-label clinical trial, COVID-19 outpatients were included by RT-PCR test or diagnosis of physicians according to the symptoms. Participants were randomly divided into intervention and control groups to receive Saliravira® package plus routine treatments of COVID-19 or routine treatments of COVID-19 alone, respectively. Saliravira® package includes tablets, nasal-sinuses spray, oral-pharynx spray, and inhaler drops. The treatment was for 10 days and followed up till 23 days after admission. RESULTS: On the 8th day, the "mean reduction rates" of viral load of the patients in the intervention group was 50% lower compared to the control group with a p-value < 0.05. The improvement of 10 out of 14 COVID-19 symptoms in the intervention group was significantly accelerated. The mean treatment duration of patients in the intervention group was 4.9 days less than the control group. In addition, no patients in the intervention group were hospitalized compared to 28% of the control group needed to be hospitalized.

Toxicity effect of sesquiterpene lactones from Jurinea gabrieliae bornm on mitochondria isolated from U87 cells.

Sesquiterpene lactones (SLs) are a typical group of secondary metabolites in asteraceae family and well-known for their biologically potential in treatment of various diseases such as cancer and inflammation. Glioblastoma (GBM) is a most common brain malignancy in adults with poor prognosis. Finding phytochemicals with potential targeting mitochondria has been suggested as an important approach for many malignancies. In this study, we purified three guaianolide-type SLs, including 8-deacyloxy-8α-(methylacryloxy)-subluteolide (A), subluteolide (B) and janerin (C) from Jurinea gabrieliae Bornm by chromatography methods. Then, mitochondrial toxicity parameters were evaluated. All three SLs selectively inhibited SDH activity in mitochondria from U87 cells but not mitochondria from normal rat brain. In addition these SLs increased ROS formation and cytochrome c release and MMP collapse only in mitochondria from U87 cells but not normal rat neurons. Our results suggest that all three SLs may act as potential agents for future development in anti-glioma therapy.

Primary Assessment of Mycosporine-Like Amino Acids Production by Two Species of Fischerella sp.

Mycosporin-like amino acids (MAAs) are a group of UV-absorbing compounds, which can be produced by various organisms such as algae and cyanobacteria, particularly if they survive in highly irradiated environments. In this study, the production of MAAs by two species of Fischerlla sp. (F5 and F14), isolated from the North of Iran, was investigated. Both species, which had previously been morphologically detected as Fisherella sp., were confirmed molecularly by sequencing the PCR amplicon of the 16S rRNA gene. The species were cultured in sterilized BG.11 medium for 21 days, then biomasses were separated, and their MAAs content was extracted by methanol and partially purified using chloroform liquid-liquid extraction. The extract was analyzed using high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS). In both species, the compounds with MAAs characteristics were observed. They had maximum absorbance (λmax) in the range of 300-400 nm, which was confirmed by the LC-MS analysis. In F5 species, the peaks with m/z 340 and 391 and in another one (F14), a peak with m/z 333.2 were recorded, that the latter might be Shinorine. In general, further analysis should be performed to elucidate the exact structural aspects of these compounds. In conclusion, both Fischerella sp. studied here were capable of producing MAAs and can be evaluated for use in sunscreen pharmaceutical and cosmetic products.

Mushrooms-Rich Preparations on Wound Healing: From Nutritional to Medicinal Attributes.

Mushrooms have a significant role in human diet as functional food and as a nutraceutical resource. The combination of its umami flavor, protein, vitamins, minerals and carbohydrates has meant that mushrooms could be considered a cheap food source for a long time in many countries. Moreover, mushrooms contain an excellent variety of bioactive metabolites that can be successful in both prevention and treatment of various human health hazards. In addition, extracts from medicinal mushrooms and their metabolites have been verified for wound treating with contribution to different mechanisms of the healing process. This review summarizes the nutritional value and composition of mushrooms, ethnobiology and ethnopharmacology, and wound healing potential.

Anti-inflammatory Activity of Bioactive Compounds from Microalgae and Cyanobacteria by Focusing on the Mechanisms of Action.

Microalgae and cyanobacteria are the potentially valuable source of bioactive compounds applied in the various industries and human usage in different fields of pharmaceutical, nutraceutical, and cosmetic disciplines. One of the interesting aspects is their application as the anti-inflammatory agents for treatment of inflammation related mal-conditions. Natural compounds are of great importance in the treatment of inflammations to reduce the reaction of immune system against pathogens, toxic compounds and damaged cells. A wide range of different metabolites with various chemical structures, including small molecules and peptides and proteins, polysaccharides, fatty acids and their derivatives have been found in microalgae and cyanobacteria which have anti-inflammatory activity. In this review, we summarized different metabolites with anti-inflammatory activity that were extracted from these microorganisms and their mechanisms. The bioactive compounds from microalgae and cyanobacteria have exhibited anti-inflammatory activity through different mechanisms acting intra- or extra- cellularly. So, they could be considered as promising anti-inflammatory agents in treatment of related diseases.

Malva species: Insights on its chemical composition towards pharmacological applications.

Malvaceae family is typical from the Mediterranean region, contains 240 genera and more than 4,200 species. They are most commonly used as ornamental plants, although they can also be conceived as a food resource and remedy for various diseases, such as digestive, respiratory, genitourinary, throat infections, and skeletal and skin disorders, as also injuries where they are profoundly applied for skin care and as antiseptic and demulcent. They also possess diuretic, lenitive, spasmolytic, and laxative effects, besides to be used as antidiarrheal. Thus, the present review provides in-depth data on Malva spp. potential applications and phytochemical composition for food and pharmaceutical industries. Habitat and cultivation conditions and the clinical reports related to its biological effects are also emphasized. Malva spp. possess a wide variety of chemical constituents (such as polysaccharides, coumarins, flavonoids, polyphenols, vitamins, terpenes, and tannins) found in different plant organs, especially in leaves and flowers, connected to their biological activity. In general, Malva spp. have rather moderate antimicrobial activity, high antiinflammatory and wound healing activities, strong antioxidant activity, and anticancer properties. Results from in vitro and in vivo experiments encourage more in-depth studies, namely clinical trials, towards to improve knowledge on the use of Malva spp. for the treatment of various health conditions in humans.

Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer.

Silymarin is a complex extract isolated from the plant Silybum marianum, widely known for its prominent antioxidant and hepatoprotective effects, although increasing evidences have reported extraordinary antiproliferative and apoptotic abilities. As a result, several signaling pathways involved in cell cycle control, cell proliferation, and cell death have been deconvoluted as critical mechanisms. In this regard, cyclin and cyclin-dependent pathways have been the most studied ones. Following that, apoptotic pathways, such as p53, Akt, STAT-3, Ras, and caspases pathways, have been extensively studied, although other mechanisms involved in inflammation and angiogenesis have also been highlighted as silymarin-likely targets in cancer therapy. Therefore, the main challenge of this review is to discuss the diverse molecular mechanisms for silymarin antiproliferative and apoptotic effects; most of them largely studied in various types of cancers so far. Clinical trials and combination therapies related to silymarin application in cancer prevention and treatment are presented as well.

Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology.

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo.

Study of Combined Ultrasound-microwave Effect on Chemical Compositions and E. coli Count of Rose Aromatic Water.

Since the rose water is used in food, pharmaceutical, and cosmetic products, its microbiological control is necessary. Conventional pasteurization methods cause undesirable changes in taste, smell, medicinal properties and nutritional value with decreasing the amount of essential oil, because of high temperatures. In this study, the effects of the microwave power, temperature, ultrasound power, and ultrasonic exposure were evaluated during rose water pasteurization process on its chemical compositions and E. coli content. In order to determine the microbial inactivation by microwave and ultrasound, E. coli at a concentration of 2 × 106 per mL was inoculated to rose aromatic water. The results showed that each variable on the inactivation of E. coli and energy consumption per microbial reduction cycle had a significant effect. The optimum values of microwave power, temperature, ultrasound power, and ultrasound exposure time were obtained 326.24 W, 43.32 °C, 100 W and 4 min, respectively. The chemical composition assessment was done by GC/MS analysis. Phenethyl alcohol is one of the main components of rose water which was completely lost in the conventional pasteurization method, while in pasteurization process by combined method, it showed an acceptable decrease as compared with raw rose water. Furthermore, the proposed method caused minimal changes in the chemical compositions of the rose water as compared to the conventional heating methods.

Biotransformation of Progesterone by Whole Cells of Filamentous Fungi Aspergillus brasiliensis.

Microbial steroid biotransformations have found a wide-reaching application for the production of more precious and functionalized compounds due to their high regio-and stereo selectivity. In this study, the possibility of using filamentous fungi Aspergillus brasiliensiscells in the biotransformation of progesterone, a C-21 steroid hormone was studied for the first time. The fungal strain was inoculated into the transformation medium supplemented with progesterone as a substrate. Biotransformation of this steroid for 7 days afforded 3 different hydroxylated metabolites: 11α-hydroxy progesterone; 14α-hydroxyprogesteroneand21-hydroxyprogesterone. The metabolites were separated by thin layer chromatography. Structure determinations of the metabolites were performed by comparing NMR, MS and IR spectra of the starting compound with those of metabolites. These results may be of industrial importance because the metabolites can be used as precursor of some steroid drugs.

Fungal transformation of androsta-1,4-diene-3,17-dione by Aspergillus brasiliensis.

BACKGROUND: The biotransformation of steroids by fungal biocatalysts has been recognized for many years. There are numerous fungi of the genus Aspergillus which have been shown to transform different steroid substances. The possibility of using filamentous fungi Aspergillus brasiliensis cells in the biotransformation of androsta-1,4-diene-3,17-dione, was evaluated. METHODS: The fungal strain was inoculated into the transformation medium which supplemented with androstadienedione as a substrate and fermentation continued for 5 days. The metabolites were extracted and isolated by thin layer chromatography. The structures of these metabolites were elucidated using (1)H-NMR, broadband decoupled (13)C-NMR, EI Mass and IR spectroscopies. RESULTS: The fermentation yielded one reduced product: 17ß-hydroxyandrost-1,4-dien-3-one and two hydroxylated metabolites: 11α-hydroxyandrost-1,4-diene-3,17-dione and 12ß-hydroxyandrost-1,4-diene-3,17-dione. CONCLUSIONS: The results obtained in this study show that A. brasiliendsis could be considered as a biocatalyst for producing important derivatives from androstadienedione.