Anti-inflammatory Activity Research Articles

Orange Peel Lactiplantibacillus plantarum: Development of A Mucoadhesive Nasal Spray with Antimicrobial and Anti-Inflammatory Activity

Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum BIA was isolated from orange peel and taxonomically identified through 16S rRNA gene sequencing. Its antibacterial activity was tested against Pseudomonas aeruginosa, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, while anti-inflammatory potential was evaluated by Griess assay. BIA genome was fully sequenced and analyzed to assess its safety. BIA was formulated in a freeze-dried matrix, containing prebiotics and cryoprotectants, to be reconstituted with a polymer solution. Solutions containing two types of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid were evaluated as resuspending media and compared in terms of pH, viscosity, and mucoadhesion ability. The biological activity of BIA formulated as nasal spray was verified together with the stability of the selected formulations. Results: L. plantarum BIA inhibited human pathogens’ growth and showed anti-inflammatory activity and a safe profile. In the best-performing formulation, the probiotic is lyophilized in 10% fructooligosaccharides, 0.1% ascorbic acid, and 0.5% lactose and reconstituted with HPMC high viscosity 1% w/v. This composition ensured the probiotic’s viability for up to six months in its dried form and one week after reconstitution. It also allowed interaction with the nasal mucosa, preserving its antimicrobial and anti-inflammatory activities. Conclusion: The developed nasal spray could become a promising formulation in the field of nasal infectious and inflammatory diseases.

Cinnamaldehyde in Focus: Antimicrobial Properties, Biosynthetic Pathway, and Industrial Applications

Trans-cinnamaldehyde (TCA), a major bioactive compound derived from cinnamon (Cinnamomum spp.), has garnered significant attention for its diverse therapeutic properties. Its broad-spectrum antimicrobial activity, targeting both Gram-positive and Gram-negative bacteria as well as various fungi, positions TCA as a potent natural antimicrobial agent. Beyond its antimicrobial effects, TCA demonstrates promising antidiabetic and anti-inflammatory activities, making it a valuable compound in medicinal and cosmetic applications. Recent studies have highlighted its role in disrupting microbial membranes, inhibiting biofilm formation, and modulating key metabolic pathways in pathogens. Furthermore, TCA has gained popularity in cosmetics due to its antimicrobial activity, antioxidant properties, and skin-friendly profile. This review provides a comprehensive overview of TCA’s antimicrobial potential, focusing on its mechanisms of action and its market and industrial applications. We also discuss the biosynthetic pathway of TCA, exploring both its natural production in cinnamon and advances in biotechnological production methods. As the demand for sustainable and natural antimicrobial agents grows, TCA emerges as a promising candidate for diverse applications. Finally, this review explores future directions for optimizing TCA production through metabolic engineering and synthetic biology approaches to meet industrial-scale demands.

Development, characterization, and assessment of PLAROsomal vesicular system of curcumin for enhanced stability and therapeutic efficacy

Abstract Background Curcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others. A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release. Result The prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%. In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR. Conclusion Furthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system. Highlights Newly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system. This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity. Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system. Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system. Graphical abstract

In-vivo evaluation of analgesic and anti-inflammatory activities of the 80% methanol extract of Acacia seyal stem bark in rodent models

Abstract Background Pain and inflammation are the major medical condition commonly addressed with traditional remedies. Acacia seyal is a traditional herb widely used in Ethiopian folk medicine for pain management. However, its effectiveness has yet to be validated through scientific or experimental research. Therefore, the current study aims at evaluating the in vivo analgesic and anti-inflammatory effects of 80% methanolic stem bark extract of Acacia seyal in rodent models. Methods After successful extractions of the stem barks of Acacia seyal with 80% methanol, the pain relieving effects of 100, 200 and 400 mg/kg extract were evaluated using acetic acid-induced writhing test and hot plate method whereas the anti-inflammatory profile was determined by carrageenan induced paw-edema model and cotton pellet induced granuloma technique. Results The 80% methanol Acacia seyal stem bark extract exhibited substantial (p < 0.001) analgesic effect in acetic acid induced writing test (p < 0.001). The plant extract also witnessed significant central analgesic effect in hot plate method beginning at 30 min with maximum % elongation time occurred at 120 min. Furthermore, the acacia stem bark extract produced anti-inflammatory effect against carrageenan induced paw-edema model. In cotton pellet induced granuloma model, the 200 and 400 mg/kg doses of the current plant material appeared to inhibit granuloma mass formation and exudate reduction significantly (p < 0.001). Conclusion The collective findings of the current study revealed that 80% methanol extracts of Acacia seyal exhibited considerable analgesic and anti-inflammatory activities, supporting the plant’s traditional use for management of pain and inflammatory disorders.

Lycopene alleviates chemotherapy-induced mucositis via enhancing intestinal barrier function and attenuating TLR4/MyD88/NF-κB signaling cascade

5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents used in treating solid tumors. Lycopene is a natural exogenous carotenoid with antioxidant, anti-inflammatory, immunomodulatory, and anticancer activity. Intestinal mucositis is a commonly encountered complication for chemotherapy. However, effective or preventive treatment for this common complication is still need to be elucidated. The current study aimed to appraise the effect of lycopene on 5-FU-induced intestinal mucositis (FUIIM). Twenty-eight male rats were divided randomly and equally into four groups: control, lycopene, FUIIM, and 5-FU + lycopene groups. Parameters for mucosal barrier integrity, redox and inflammatory status, and apoptosis were immunoassayed in addition to histological assessment. Decreased body weight, significantly impaired redox status, increased caspase 3 level, toll-like receptor (TLR) 4 level, myd88 and NF-κB expression. However, decreased Bcl-2, and Ki-67 expression were detected in 5-FUIIM group. Furthermore, impairment in intestinal barrier integrity, represented by decreased Occludin and claudin1 levels with impaired histological features and ultrastructural features, were also detected. Meanwhile, lycopene co-administration protected against weight loss, heightened oxidative stress, apoptosis, inflammation, disturbed intestinal barrier integrity, and impaired histological and ultrastructure features. In conclusion, lycopene significantly improved intestinal mucositis, barrier integrity and gut toxicity induced by 5-FU in rats.

Psycho-Neuro-EndocrinE-Immunology Therapy of Cancer, Autoimmunity, Geriatric Disorders, Covid-19, and Hypertension.

Despite the great number of experimental investigations in the area of psycho-neuro-endocrine-immunology showing that endocrine, nervous, and immune systems cannot be in vivo physiologically separated, the diagnosis and therapies of the pathologies of these three functional biological systems continue to be separately performed from a clinical practice point of view. The separation between experimental and clinical medicine became dramatic after the discovery of more than 10 human molecules provided by anti-inflammatory and antitumor activity, completely devoid of any toxicity, which may be subdivided into three fundamental classes, consisting of the pineal indole, beta-carboline, and methoxy-kynuramine hormones. Moreover, human systemic diseases, including cancer, autoimmunity, and cardiovascular pathologies, despite their different pathogenesis and symptomatology, are commonly characterized by a progressive decline in the endogenous production of pineal hormones, endocannabinoids, and Ang 1-7, with a consequent inflammatory status and diminished natural resistance against cancer. Then the evaluation of the functional status of the pineal gland, the endocannabinoid system, and ACE2-Ang 1-7 axis should have to be included within the laboratory analyses for the systemic diseases. Finally, the correction of cancer- and autoimmunity-related neuroimmune and neuroendocrine alterations could influence the clinical course of systemic diseases. In fact, preliminary clinical results would demonstrate that the neuroimmune regimen with pineal hormones, cannabinoids, and Ang 1-7 may allow clinical benefits also in patients affected by systemic pathologies, including cancer, autoimmunity, and cardiovascular diseases, who did not respond to the standard therapies.

Anti- Inflammatory Activities Of The Methanol Leaf Extract And Fractions Of Elaesis Guineensis In In-Vivo Animals

Abstract Objective Objective of this paper is to investigate the preliminary anti-inflammatory property of the leaves and its fractions of Elaesis guineensis using egg induced albumin and formaldehyde induced arthritis models in rats. Method Egg albumin induced inflammation was induced by sub-plantar injection of 0.1 ml of fresh undiluted egg albumin. The volume of distilled water displaced by the treated paw was measured at 0.5,1, 2, 3, 4, 5, and 6 hours after induction of inflammation. Formaldehyde-induced arthritis was induced after 30 min by sub-plantar injection of 0.1 ml of 2.5% formaldehyde solution and was repeated on day 3. Arthritis was assessed by measuring the volume of distilled water displaced by the paw before induction of arthritis and once every day for ten days, starting from day one, after induction of arthritis. Results The acute toxicity test revealed that the plant extract was safe even at 5000 mg/kg dose level. The methanol extract (ME) showed a dose-dependent inhibition of egg albumin-induced acute inflammation that peaked at the dose of 200 mg/kg, while the fractions of the extract showed that the hexane and ethyl acetate fractions had the highest activity during the experiment. Similarly, the crude extract of the formaldehyde induced arthritis showed a dose-dependent inhibition making the 200 mg/kg the most active dose level. Additionally, it was observed that among the fractions of the extract the hexane fraction (HF) showed the most significant inhibitory activity when compared to other fractions Conclusion this study establishes that the methanol leaf extract and fractions ofElaesis guineensis possess significant anti-inflammatory activity

Formulation and Evaluation of Polyherbal Soap

The aim of the study is to formulate and evaluate Polyherbal soap using coconut oil, beeswax, NaOH(lye), Glycerine, Neem, aloe vera, Turmeric, Tulsi, Sandalwood powder, orange peel powder, Multani mitti, Reetha, Honey and Vitamin E capsule. The herbal formulation was prepared then evaluation of the analysis of Physical parameter, pH, Foam height, Foam retention time, Moiture content, Alcohol insoluble matter etc. Various study found that, these herbal plant extract proven to anti-bacterial activity, anti-inflammatory activity, anti-fungal activity etc. The finding for the herbal soap reveals that these soaps are cost effective, convenient, natural foam generate on application, not exhibit any skin irritation and less or no side effect. Keywords: Polyherbal soap, Neem, Aloevera, Turmeric, Moisture content.

Development of a Water-Soluble Nanomicellar Formulation Loaded with Trans-Resveratrol Using Polyethylene Glycol Monostearate for the Treatment of Intracerebral Hemorrhage

Background/Objectives: Trans-resveratrol (Res) has been reported to possess many biological activities, including neuroprotective effects, owing to its anti-inflammatory and antioxidant properties. However, Res has very low water solubility, which limits its therapeutic application. In this work, we formulated water-soluble micellar formulations incorporating Res using polyethylene glycol monostearate (stPEG). Methods: These formulations (stPEG/Res) were developed using five types of stPEG containing 10, 25, 40, 55 and 140 PEG repeat units. The formulations were characterized for Res content, water solubility, particle size, zeta potential, precipitation, biodistribution, and efficacy against neuronal and motor dysfunction in intracerebral hemorrhage (ICH). Results: Intravenous administration of stPEG40/Res, which demonstrated particle size, water solubility, and biodistribution properties suitable for intravenous administration, suppressed neurological and motor dysfunction following in a collagenase-induced ICH mouse model. These effects were inhibited by zinc protoporphyrin-9, an inhibitor of the antioxidant enzyme heme oxygenase-1, suggesting that Res contributes to antioxidant enzyme expression and anti-inflammatory activity. Conclusions: The stPEG/Res micellar formulation developed in this study may offer a promising therapeutic approach for ICH treatment.

An in vivo and in silico probing of the protective potential of betaine against sodium fluoride-induced neurotoxicity.

Excessive fluoride exposure beyond the tolerable limit may adversely impacts brain functionality. Betaine (BET), a trimethyl glycine, possesses antioxidant, anti-inflammatory and anti-apoptotic functions, although the underlying mechanisms of the role of BET on fluoride-induced neurotoxicity remain unelucidated. To assess the mechanism involved in the neuro-restorative role of BET on behavioural, neurochemical, and histological changes, we employed a rat model of sodium fluoride (NaF) exposure. Animals were treated with NaF (9mg/kg) body weight (bw) only or co-treated with BET (50 and 100mg/kg bw) orally uninterrupted for 28 days. We obtained behavioural phenotypes in an open field, performed negative geotaxis, and a forelimb grip test, followed by oxido-inflammatory, apoptotic, and histological assessment. Behavioural endpoints indicated lessened locomotive and motor and heightened anxiety-like performance and upregulated oxidative, inflammatory, and apoptotic biomarkers in NaF-exposed rats. Co-treatment with BET significantly enhanced locomotive, motor, and anxiolytic performance, increased the antioxidant signalling mechanisms and demurred oxidative, inflammatory, and apoptotic biomarkers and histoarchitectural damage in the cerebrum and cerebellum cortices mediated by NaF. The in-silico analysis suggests that multiple hydrogen bonds and hydrophobic interactions of BET with critical amino acid residues, including arginine (ARG380 and ARG415) in the Keap1 Kelch domain, which may disrupt Keap1-Nrf2 complex and activate Nrf2. This may account for the observed increased in the Nrf2 levels, elevated antioxidant response and enhanced anti-inflammatory response. The BET-Keap1 complex was also observed to exhibit structural stability and conformational flexibility in solvated biomolecular systems, as indicated by the thermodynamic parameters computed from the trajectories obtained from a 100 ns full atomistic molecular dynamics simulation. Therefore, BET mediates neuroprotection against NaF-induced cerebro-cerebellar damage through rats' antioxidant, anti-inflammatory, and anti-apoptotic activity, which molecular interactions with Keap1-Nrf2 may drive.

A review on ethnobotany, phytochemistry, and pharmacology of the genus Duhaldea DC

The botanical drugs of genus Duhaldea DC. have been traditionally utilized in folk medicine for the treatment of a wide array of illnesses, encompassing fractures, bone wounds, carbuncles and poisoning, bronchitis, bruises, giddy with hypertension of qi, and lung deficiency cough. The genus Duhaldea DC. comprises 15 species widespread in Central, East, and Southeast Asia and 7 species (2 endemic) in China. The review aims to provide a systematic overview of ethnopharmacology, phytochemistry, and pharmacology of Duhaldea DC. and to explore the future therapeutic potential and scientific potential of this genus. The data were systematically collected from books and scientific databases such as PubMed, Web of Science, Google Scholar, CNKI, and doctoral and master’s theses. To date, a total of 352 metabolites have been isolated from this genus, and terpenoids, flavonoids, phenylpropanoids, and inositol angelates are the primary contributors to the pharmacological activities of Duhaldea DC. The crude extracts and isolated phytochemical metabolites from this genus have been shown to exhibit various pharmacological activities, including anti-inflammatory, antimicrobial, anti-osteoporotic, anticancer, and antioxidant activities. Despite notable advancements in our understanding of the chemical constituents and pharmacological properties of Duhaldea DC., it is absolutely crucial to conduct additional research into the pharmacology and toxicology of these species to definitively ascertain their safety, efficacy, and quality.

The potential of lactoferrin as antiviral and immune-modulating agent in viral infectious diseases

Emerging infectious diseases are caused by unpredictable viruses with the dangerous potential to trigger global pandemics. These viruses typically initiate infection by utilizing the anionic structures of host cell surface receptors to gain entry. Lactoferrin (Lf) is a multifunctional glycoprotein with multiple properties such as antiviral, anti-inflammatory and antioxidant activities. Due to its cationic structure, Lf naturally interacts with certain host cell receptors, such as heparan sulfate proteoglycans, as well as viral particles and other receptors that are targeted by viruses. Therefore, Lf may interfere with virus-host cell interactions by acting as a receptor competitor for viruses. Herein we summarize studies in which this competition was investigated with SARS-CoV-2, Zika, Dengue, Hepatitis and Influenza viruses in vitro. These studies have demonstrated not only Lf’s competitive properties, but also its potential intracellular impact on host cells, such as enhancing cell survival and reducing infection efficiency by inhibiting certain viral enzymes. In addition, the immunomodulatory effect of Lf is highlighted, as it can influence the activity of specific immune cells and regulate cytokine release, thereby enhancing the host’s response to viral infections. Collectively, these properties promote the potential of Lf as a promising candidate for research in viral infectious diseases.

Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease

The defense mechanisms of the vertebrate brain against infections are at the forefront of immunological studies. Unlike other body parts, the brain not only fends off pathogenic infections but also minimizes the risk of self-damage from immune cell induced inflammation. Some neuropeptides produced by either nerve or immune cells share remarkable similarities with antimicrobial peptides (AMPs) in terms of size, structure, amino acid composition, amphiphilicity, and net cationic charge. These similarities extend to a wide range of antibacterial activities demonstrated in vitro, effectively protecting nerve tissue from microbial threats. This review systematically examines 12 neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), orexin-B (ORXB), ghrelin, substance P (SP), adrenomedullin (AM), calcitonin-gene related peptide (CGRP), urocortin-II (UCN II), neuropeptide Y (NPY), NDA-1, and catestatin (CST), identified for their antimicrobial properties, summarizing their structural features, antimicrobial effectiveness, and action mechanisms. Importantly, the majority of these antimicrobial neuropeptides (9 out of 12) also possess significant anti-inflammatory properties, potentially playing a key role in preserving immune tolerance in various disorders. However, the connection between this anti-inflammatory property and the brain’s infection defense strategy has rarely been explored. Our review suggests that the combined antimicrobial and anti-inflammatory actions of neuropeptides could be integral to the brain’s defense strategy against pathogens, marking an exciting direction for future research.

Discovery of Chalcone Derivatives as Bifunctional Molecules with Anti-SARS-CoV-2 and Anti-inflammatory Activities.

Danshensu extracted with traditional Chinese medicine Salvia miltiorrhiza has a wide range of bioactivities. Danshensu containing a catechol moiety has a moderate inhibitory effect on SARS-CoV-2 3CLpro (IC50 = 2.2 μM) by a reversible covalent interaction and exhibits good anti-inflammatory activity. To enhance the inhibitory activity, we introduced Michael receptors into the side chain of danshensu as a possible covalent warhead and blocked the covalent binding sites of catechol moiety to yield chalcone derivatives. The resulting chalcone derivatives, A4 and A7, were found to inhibit SARS-CoV-2 3CLpro in vitro with IC50 values of 83.2 and 261.3 nM, respectively. Furthermore, A4 and A7 inhibit viral replication in the SARS-CoV-2 replicon system with EC50 values of 19.9 and 11.7 μM, respectively. Time-dependent inhibition experiment and mass spectrometry show that A4 acted as a noncovalent mixed inhibitor, while A7 likely binds covalently at Cys145. The interaction mechanism between SARS-CoV-2 3CLpro and A4 or A7 was characterized by molecular docking studies. Additionally, both A4 and A7 demonstrated potent anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. These promising results suggest that chalcone derivatives A4 and A7 can serve as bifunctional molecules with both antivirus and anti-inflammatory properties.

The bioactive constituents from the fruits of Elaeagnus angustifolia L.

Multiple spectroscopic, chromatographic, and chemical reaction methods were combined to investigate the chemical components in the fruits of Elaeagnus angustifolia L. As results, thirty-two compounds were obtained from it as natural products. Six of them, elangphenosides A (1), B (2), C (3) and D (4), elangmegastigmanoside A (5), and elangorganic acid A1 (6) were retrieved by Scifinder as previously undescribed ones. Additionally, a previously undescribed artificial product, elangorganic acid A2, as well as a known artificial one, (3R) 5-ethoxy-3-(ethoxycarbonyl)-3-hydroxy-5-oxopentanoic acid, were yielded. Following the phytochemical investigation, LC-MS analysis was employed to conduct a systematical characterization of the constituents from E. angustifolia fruits. Ultimately, fifty-six compounds, including seventeen phenols, one ionone, twenty-four triterpenes, and fourteen other ones, were unambiguously detected and identified. Moreover, in vitro anti-inflammatory activity screening of forty-four natural compounds presented in E. angustifolia fruits was performed by using the LPS-induced RAW264.7 cell model. Twenty-six compounds, including phenols, organic acids, and other compounds, showed assignable activity. Furthermore, their structure-activity relationships were summarized. Combined with the previous research work in our lab, triterpenes, phenols, and organic acids were speculated to be key components during the E. angustifolia fruits exerting anti-inflammatory activity. In summary, this article fully explored the chemical composition of E. angustifolia fruits, assayed their in vitro NO production inhibitory effects, greatly expanding its material foundation and laying a solid foundation for further research and development.

Protective effect of maltol on pathological response of cardiomyocyte in dystrophic mice.

Heart diseases are a significant contributor to global morbidity and mortality, and despite their diverse and complex mechanisms, treatment options remain limited. Maltol, a natural compound with antioxidant and anti-inflammatory activities, exhibits potential for addressing this need. This study evaluates the cardioprotective effects of maltol in isoproterenol (ISO)-induced cardiac stress models and Duchenne muscular dystrophy (DMD). Maltol's cardiac cytotoxicity was assessed in rodent (H9c2) and human (AC16) cells and compared with that of dapagliflozin to illustrate its cardiac safety. In ISO-induced stress models, maltol significantly reduced hypertrophic markers and inflammation while enhancing autophagy and antioxidant pathways. In the mdx mice, a DMD model, maltol treatment improved cardiac contractility and reduced pathogenic remodeling. Enhanced phosphorylation of phospholamban and trends toward higher SERCA2a expression indicated enhanced Ca2+ handling, which is crucial in DMD cardiomyopathy. This study demonstrated that maltol has the potential to provide therapeutic benefits for DMD and other cardiac conditions characterized by hypertrophy and inflammation, as evidenced by its well-known antioxidant properties, low cytotoxicity, and capacity to enhance cardiac function and Ca2+ handling.

Spiro-fused indoline-quinazoline hybrids as smart bombs against TNF-α-mediated inflammation.

Inflammation is central to numerous diseases, highlighting the need for new anti-inflammatory agents. This study explores the potential of novel spirofused indoline-quinazoline hybrids (4a-p) as anti-inflammatory compounds, inspired by a spiroisatin analogue (VI) that showed modest TNF-α inhibition. We aimed to enhance activity by modifying the isatin scaffold: first, introducing N-alkylation (propyl, butyl, or isobutyl) to improve hydrophobic interactions within the TNF-α dimer active site; second, adding halogens (F, Cl, Br) at the 5-position to increase lipophilicity. Anti-inflammatory activity against TNF-α was confirmed in-vivo for all synthesized analogues, with 4b, 4e, 4 k, and 4n emerging as the top candidates. Further studies on these four compounds assessed their analgesic effects, as well as their impact on PGE2, NF-κB, paw thickness, and paw weight. In-vitro analyses revealed nanomolar TNFR2-TNF-α binding inhibition for the four leads. Safety evaluations included histopathology, ulcerogenic potential, kidney and liver functions, and acute hemotoxicity. In-silico studies examined drug-likeness, pharmacokinetics, and TNF-α dimer interactions. These results suggest that the four lead compounds possess promising profiles compared to standard therapies.

Sequential fermentation of Ginkgo biloba seeds by Bacillus subtilis natto and Lactobacillus plantarum enhanced nutrition, flavor and lipid-lowering activity.

Ginkgo biloba seeds (GBS) are rich in flavonoids, proteins and reducing sugar, and have been consumed as food and medicinal nuts for thousands of years. However, the presence of ginkgotoxins and their poor palatability limit people's consumption of them. This study used solid-state fermentation with Bacillus subtilis natto and Lactobacillus plantarum to enhance the safety and benefits of GBS. Optimized fermentation conditions increased the content of beneficial components like total flavonoids, soluble protein and reducing sugar while eliminating unpleasant odors (isoamyl aldehyde and hexanal) and reducing the toxin 4'-O-methylpyridoxine by 91.17%. Fermentation of GBS powder can significantly enhance its anti-inflammatory and antioxidant activities in vitro (P < 0.001). Furthermore, it exhibits a dose-dependent effect within a certain concentration range. Mixed fermentation (FBnLp) was evaluated for its effects on obesity and metabolic syndrome in mice fed a high-fat diet. FBnLp significantly reduced body and liver weight gain, prevented dyslipidemia and decreased inflammatory and oxidative stress compared to unfermented GBS. Histological analysis showed that FBnLp improved liver health by reducing fat accumulation and preventing non-alcoholic fatty liver disease. Meanwhile, it was found that feeding FBnLp increased the expression of CPT-1α, which regulates energy expenditure and fat breakdown, and downregulated the expression of SREBP-1c, FAS and ACC, which regulate fat synthesis. This research provides new insights and technological support for the application and development of FBnLp as a functional product, addressing key issues in its use and industry growth. © 2024 Society of Chemical Industry.

The Underrepresented Quinolinone Alkaloids in Genera Penicillium and Aspergillus: Structure, Biology, and Biosynthetic Machinery.

Quinolone alkaloids are N-heterocycles with extensive structural diversity, mainly derived from in fungi from anthranilic acid and amino acids as precursors with a wide range of biological activities as antifungal, antimicrobial, anti-inflammatory, and insecticidal activities. The quinolone basic skeleton comprised of either 2-quinolones or 4-quinolones generated more than one hundred compounds. Several reviews discussed quinolones; particularly, the fluoroquinolones, yet few studies tackled natural quinolones. Many of these quinolones were not assayed for their antimicrobial potential despite their unique stereospecificity, which can supersede synthetic quinolones if their discovery is coupled with OMICS techniques, biochemical and molecular strategies as heterologous expression to maximize their yield. Herein, we conducted a comprehensive review of the quinolone's family in Aspergillus and Penicillium species, the exclusive producers of quinolones whether they are soil, endophytic or marine derived highlighting their isolation, chemical structures, pharmacological effects, structure activity relationships if any, and biosynthetic machinery. We believe that our initiative will pave the way for further development of natural quinolones as future antimicrobial agents.

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism.

Pristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.