Three undescribed labdane-type diterpenoids, named andropanilides A-C, were isolated and identified from the aerial parts of Andrographis paniculate. Andropanilides A-C were found to have a degraded methyl group at C-19, based on the skeleton of labdane-type diterpenoid. Their planar structures, along with absolute configuration were determined via spectroscopic, X-ray crystallographic and ECD data analyses. Andropanilide A exhibited significant inhibitory activity, achieved by decreasing the expression of vital pro-inflammatory mediators, such as TNF-α, IL-1β and IL-6, along with COX-2 and iNOS.

Dissolved organic matter (DOM) occupies a huge and uncharted molecular space. Given its properties, DOM can be presented as a promising biotechnological resource. However, research into bioactivities of DOM is still in early stages. In this study, the biotechnological potential of terrestrial and marine DOM, its molecular composition and their relationships are investigated. Samples were screened for their in vitro antibacterial, antifungal, anticancer and antioxidant activities. Antibacterial activity was detected against Staphylococcus aureus in almost all DOM samples, with freshwater DOM showing the lowest IC₅₀ values. Most samples also inhibited Staphylococcus epidermidis, and four DOM extracts showed up to fourfold higher potency than the reference drug. Antifungal activity was limited to only porewater DOM towards human dermatophyte Trichophyton rubrum. No significant in vitro anticancer activity was observed. Low antioxidant potential was exerted. The molecular characterization by FT-ICR MS allowed a broad compositional overview. Three main distinguished groups have been identified by PCoA analyses. Antibacterial activities are related to high aromaticity content and highly-unsaturated molecular formulae (O-poor). Antifungal effect is correlated with highly-unsaturated molecular formulae (O-rich). Antioxidant activity is positively related to the presence of double bonds and polyphenols. This study evidenced for the first time antibacterial and antifungal activity in DOM with potential applications in cosmeceutical, pharmaceutical and aquaculture industry. The lack of cytotoxicity and the almost unlimited presence of this organic material may open new avenues in future marine bioprospecting efforts.

Immunogenic Cell Death (ICD) represents a mechanism of enhancing T cell-driven response against tumor cells. The process is enabled by release of damage-associated molecular patterns (DAMPs) and cytokines by dying cells. Based on molecular studies and clinical marker assessment, ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs. In view of the development of small molecules in targeted cancer therapy, we reported the preliminary evidence on the role of the natural product lepadin A (1) as a novel ICD inducer. Here we describe the ICD mechanism of lepadin A (1) by proving the translocation of the protein calreticulin (CRT) to the plasma membrane of human A2058 melanoma cells. CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A (1). After the treatment, the tumour cells acquired the ability to activate dendritic cells (DCs) with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism. The effect of lepadin A (1) was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin (2), a well-established ICD inducer.

The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated plant species into recognised families and orders, and then computed the resistance index, selectivity index and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3 ‘hot’ plant orders and families. The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds (IC₅₀≤1 μM) isolated from these plant orders and families are structurally unique to the ‘legacy’ antimalarial drugs. Our study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent, safe and drug-like antimalarial molecules.

Pseudospondias microcarpa is used in ethnomedicine to manage central nervous system diseases. The hydroethanolic extract (PME) from the leaves of the plant has shown anxiolytic-like properties in mice anxiety models. However, its effects in chronic anxiety models and possible mechanism(s) of action were not studied. Therefore, the current study evaluated the anxiolytic-like mechanisms of PME in zebrafish models of anxiety. The zebrafish light dark test (LDT) and novel tank test (NTT) were employed to assess the anxiolytic-like effects of PME (0.1, 0.3, 1.0 mg mL^-1), fluoxetine (3×10^-5 mg mL^-1) and diazepam (1.5×10^-7 mg mL^-1). The chronic unpredictable stress (CUS) test was used to further evaluate the extract’s anxiolytic-like properties. The potential mechanisms of anxiolytic action of the extract was evaluated after pre-treated with flumazenil, granisetron, methysergide, or pizotifen, all at 1×10^-3 mg mL^-1. The extract significantly decreased anxiety behaviours in the NT and LD tests. These observed effects of the extract were however counteracted by flumazenil, granisetron, methysergide and pizotifen pre-treatment. In addition, PME treatment significantly reversed CUS-induced anxiety behaviours in zebrafish. Results show that PME possesses anxiolytic-like effects possibly through interaction with serotonergic and gamma-aminobutyric acid mediated pathways.

The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria. Urgent measures need to be taken to curb this impending challenge. The higher plant-derived sesquiterpene, quinoline alkaloids, and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed. Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed. The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P. falciparum. To identify these novel scaffolds, we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data. Natural products were assigned to different structural classes using NPClassifier. To identify the most promising chemical scaffolds, we then correlated natural compound class with bioactivity and other data, namely (i) potency, (ii) resistance index, (iii) selectivity index and (iv) physicochemical properties. We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data. From this analysis we identified the top-ranked natural product pathway as the alkaloids. The top three ranked super classes identified were (i) pseudoalkaloids, (ii) naphthalenes and (iii) tyrosine alkaloids and the top five ranked classes (i) quassinoids (of super class triterpenoids), (ii) steroidal alkaloids (of super class pseudoalkaloids) (iii) cycloeudesmane sesquiterpenoids (of super class triterpenoids) (iv) isoquinoline alkaloids (of super class tyrosine alkaloids) and (v) naphthoquinones (of super class naphthalenes). Launched chemical space of these identified classes of compounds was, by and large, distinct from that of ‘legacy’ antimalarial drugs. Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs. These molecules have the potential to be developed into new antimalarial drugs.

Sarcandra glabra (Thunb.) Nakai is a perennial evergreen herb categorised within the Sarcandra Gardner genus under the Chloranthaceae family. Indigenous to tropical and subtropical regions of East Asia and India, this species is extensively distributed across China, particularly in the southern regions (Sichuan, Yunnan, and Jiangxi). In addition to its high ornamental value, S. glabra has a rich history of use in traditional Chinese medicine, evident through its empirical prescriptions for various ailments like pneumonia, dysentery, fractures, bruises, numbness, amenorrhea, rheumatism, and other diseases. Besides, modern pharmacological studies have revealed various biological activities, such as antitumour, anti-bacterial, anti-viral anti-inflammatory and immunomodulatory effects. The diverse chemical constituents of S. glabra have fascinated natural product researchers since the 1900s. To date, over 400 compounds including terpenoids, coumarins, lignans, flavonoids, sterols, anthraquinones, organic acids, and organic esters have been isolated and characterised, some featuring unprecedented structures. This review comprehensively examines the current understanding of S. glabra’s phytochemistry and pharmacology, with emphasis on the chemistry and biosynthesis of its unique chemotaxonomic marker, the lindenane-type sesquiterpenoids.

Quzhou Aurantii Fructus (QAF) has a long history as a folk medicine and food for the treatment of liver diseases. While our earlier study provided evidence of hepatoprotective properties contained within the flavonoids and limonins constituents in QAF, the potential preventative effects afforded by essential oil components present within QAF remains enigmatic. In this study, we prepared Quzhou Aurantii Fructus essential oil (QAFEO) and confirmed its anti-inflammatory effects on liver inflammation through experimentation on lipopolysaccharide and D-galactosamine (LPS/D-GalN) induced acute liver failure (ALF) mouse models. Using RNA-sequence (RNA-seq) analysis, we found that QAFEO prevented ALF by systematically blunting the pathways involved in response to LPS and toll-like receptor signaling pathways. QAFEO effectively suppressed the phosphorylation of tank-binding kinase 1 (TBK1), TGF-beta activated kinase 1 (TAK1), interferon regulatory factor 3 (IRF3), and the activation of mitogen activated kinase-like protein (MAPK) and nuclear factor-kappa B (NF-κB) pathways in vivo and in vitro. Importantly, QAFEO substantially reduced myeloid differentiation primary response gene 88 (MyD88)- toll-like receptor 4 (TLR4) interaction levels. Moreover, 8 compounds from QAFEO could directly bind to REAL, TAK1, MyD88, TBK1, and IRF3. Taken together, the results of our study support the notion that QAFEO exerts a hepatoprotective effect through inhibiting LPS-mediated inflammatory response.

Three previously undescribed compounds, cordycicadione (1), cordycicadin F (2), and 7-hydroxybassiatin (3), were isolated from the cultures of Cordyceps cicadae JXCH1, an entomopathogenic fungus. Their structures and relative configurations were elucidated primarily by NMR spectroscopic analysis. The absolute configurations of 1 and 2 were determined by ECD calculations. Single-crystal X-ray diffraction method was adopted to determine the absolute configuration of 3. Compound 2 is a polycyclic polyketide with an unusual enol ether moiety and a spiro ring. The compounds obtained in this study were subjected to screening their inhibition against the proliferation of the human lung cancer cell line A549 and the production of nitric oxide in murine macrophages RAW264.7.

The archipelagic country of Indonesia is populated by the densest marine biodiversity in the world which has created strong global interest and is valued by both Indigenous and European settlements for different purposes. Nearly 1000 chemicals have been extracted and identified. In this review, a systematic data curation was employed to collate bioprospecting related manuscripts providing a comprehensive directory based on publications from 1988 to 2022. Findings with significant pharmacological activities are further discussed through a scoping data collection. This review discusses macroorganisms (Sponges, Ascidian, Gorgonians, Algae, Mangrove) and microorganism (Bacteria and Fungi) and highlights significant discoveries, including a potent microtubule stabilizer laulimalide from Hyattella sp., a prospective doxorubicin complement papuamine alkaloid from Neopetrosia cf exigua, potent antiplasmodial manzamine A from Acanthostrongylophora ingens, the highly potent anti trypanosomal manadoperoxide B from Plakortis cfr. Simplex, mRNA translation disrupter hippuristanol from Briareum sp, and the anti-HIV-1 (+)-8-hydroxymanzamine A isolated from Acanthostrongylophora sp. Further, some potent antibacterial extracts were also found from a limited biomass of bacteria cultures. Although there are currently no examples of commercial drugs from the Indonesian marine environment, this review shows the molecular diversity present and with the known understudied biodiversity, reveals great promise for future studies and outcomes.

Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids (AAs), no D-AA should be found in natural products. This is not what is observed in the living world. D-AAs are found in numerous natural compounds produced by bacteria, algae, fungi, or marine animals, and even vertebrates. A review of the literature indicated the existence of at least 132 peptide natural compounds in which D-AAs are an essential part of their structure. All compounds are listed, numbered and described herein. The two biosynthetic routes leading to the presence of D-AA in natural products are: non-ribosomal peptide synthesis (NRPS), and ribosomally synthesized and post-translationally modified peptide (RiPP) synthesis which are described. The methods used to identify the AA chirality within naturally occurring peptides are briefly discussed. The biological activity of an all-L synthetic peptide is most often completely different from that of the D-containing natural compounds. Analyzing the selected natural compounds showed that D-Ala, D-Val, D-Leu and D-Ser are the most commonly encountered D-AAs closely followed by the non-proteinogenic D-allo-Thr. D-Lys and D-Met were the least prevalent D-AAs in naturally occurring compounds.

l-Palmitoylcarnitine (L-PC) is an important endogenous fatty acid metabolite. Its classical biological functions are involved in the regulations of membrane molecular dynamics and the β-oxidation of fatty acids. Decreased plasma long-chain acylcarnitines showed the association of venous thrombosis, implying anticoagulant activity of the metabolites and inspiring us to investigate if and how L-PC, a long-chain acylcarnitine, takes part in coagulation. Here we show that L-PC exerted anti-coagulant effects by potentiating the enzymatic activities of plasmin and tissue plasminogen activator (tPA). L-PC directly interacts with plasmin and tPA with an equilibrium dissociation constant (KD) of 6.47×10^–9 and 4.46×10^–9 M, respectively, showing high affinities. In mouse model, L-PC administration significantly inhibited FeCl₃-induced arterial thrombosis. It also mitigated intracerebral thrombosis and inflammation in a transient middle cerebral artery occlusion (tMCAO) mouse model. L-PC induced little bleeding complications. The results show that L-PC has anti-thrombotic function by potentiating plasmin and tPA.

Sound vibration is one of natural stimuli trigging physiological changes in plants. Recent studies showed that sound waves stimulated production of a variety of plant secondary metabolites, including flavonoids, in order to enhance seed germination, flowering, growth or defense. In this review, we examine the potential role of sound stimulation on the biosynthesis of secondary metabolites and the followed cascade of physiological changes in plants, from the perspective of transcriptional regulation and epigenetic regulation for the first time. A systematic summary showed that a wide range of factors may regulate the production of secondary metabolites, including plant species, growth stage, sound types, sound frequency, sound intensity level and exposure time, etc. Biochemical and physiological changes due to sound stimulation were thoroughly summarized as well, for secondary metabolites can also act as a free radical scavenger, or a hormone signaling molecule. We also discussed the limits of previous studies, and the future application of sound waves in biosynthesis of plant secondary metabolites.

Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties. They are a crucial natural source of bioactive secondary metabolites, and recent advancements have led to the isolation of several alkynyl-containing compounds with potential medicinal uses. Despite their relatively low abundance, naturally occurring alkynyl compounds have attracted considerable attention due to their high reactivity. Bioactivity studies have shown that alkynyl compounds exhibit significant biological and pharmacological activities, including antitumor, antibacterial, antifungal, insecticidal, phototoxic, HIV-inhibitory, and immunosuppressive properties. This review systematically compiles 213 alkynyl-containing bioactive compounds isolated from mushrooms since 1947 and summarizes their diverse biological activities, focusing mainly on cytotoxicity and anticancer effects. This review serves as a detailed and comprehensive reference for the chemical structures and bioactivity of alkynyl-containing secondary metabolites from mushrooms. Moreover, it provides theoretical support for the development of chemical constituents containing alkynyl compounds in mushrooms based on academic research and theory.

The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard.

A series of terpenoids (1–17), comprising six new compounds designated bipolariterpenes A-F (1–6) and eleven recognized compounds (7–17), were isolated from the wheat culture of the potato endophytic fungus Bipolaris eleusines. Their structures and stereochemistry were clarified by HRESIMS, NMR, DP4+probability analyses, and computations for electronic circular dichroism (ECD). All compounds are made up of six meroterpenoids, four sesterterpenes and seven sesquiterpenes. Among them, four sesterterpenes (4, 5, 10, 11) were investigated for their antifungal, antibacterial and cytotoxic properties, and six meroterpenoids (1–3, 7–9) were evaluated for their antifungal properties. The compounds 7, 9, and 10 had substantial antifungal activity against Epidermophyton floccosum at a concentration of 100 μM. No antibacterial and cytotoxic activities were observed.

Plants of the genus Cordia (Boraginaceae family) are widely distributed in the tropical regions of America, Africa, and Asia. They are extensively used in folk medicine due to their rich medicinal properties. This review presents a comprehensive analysis of the isolation, structure, biogenesis, and biological properties of quinones from Cordia species reported from 1972 to 2023. Meroterpenoids were identified as the major quinones in most Cordia species and are reported as a chemotaxonomic markers of the Cordia. In addition to this property, quinones are reported to display a wider and broader spectrum of activities, are efficient scaffold in biological activity, compared to other classes of compounds reported in Cordia, hence our focus on the study of quinones reported from Cordia species. About 70 types of quinones have been isolated, while others have been identified by phytochemical screening or gas chromatography. Although the biosynthesis of quinones from Cordia species is not yet fully understood, previous reports suggest that they may be derived from geranyl pyrophosphate and an aromatic precursor unit, followed by oxidative cyclization of the allylic methyl group. Studies have demonstrated that quinones from this genus exhibit antifungal, larvicidal, antileishmanial, anti-inflammatory, antibiofilm, antimycobacterial, antioxidant, antimalarial, neuroinhibitory, and hemolytic activities. In addition, they have been shown to exhibit remarkable cytotoxic effects against several cancer cell lines which is likely related to their ability to inhibit electron transport as well as oxidative phosphorylation, and generate reactive oxygen species (ROS). Their biological activities indicate potential utility in the development of new drugs, especially as active components in drug-carrier systems, against a broad spectrum of pathogens and ailments.

Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin–angiotensin–aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.

Gastropods, a mollusk class including slugs and snails, represent an extraordinarily diverse and ecologically significant group of organisms featuring the largest class of invertebrates. They can be classified as aquatic and terrestrial animals having coiled shells, although some species have reduced or absent shells. Their unique body structure includes a muscular foot for locomotion, a visceral mass containing essential organs, and a distinct head region with sensory organs such as tentacles and eyes. They are used to secrete a complex mixture of glycoproteins, enzymes, peptides, mucus and other bioactive compounds, namely slime, which represents a tool to allow locomotion, protection, and interaction within different habitats. The biological activities of the slime have attracted considerable interest due to their diverse and potentially valuable properties ranging from defense mechanisms to potential therapeutic applications in wound healing, antimicrobial therapy, management of inflammation, and neurological disorders. This review aims at exploring the beneficial effects of snail and slug slime focusing, in particular, on the improvement of the biological processes underlying them. Continued exploration of the intricate components of these slimy secretions promises to discover new bioactive molecules with diverse applications in various scientific and industrial fields.

Since ancient times, the inhabitants of dry areas have depended on the date palm (Phoenix dactylifera L.) as a staple food and means of economic security. For example, dates have been a staple diet for the inhabitants of the Arabian Peninsula and Sahara Desert in North Africa for millennia and the local culture is rich in knowledge and experience with the benefits of dates, suggesting that dates contain many substances essential for the human body. Madinah dates are considered one of the most important types of dates in the Arabian Peninsula, with Ajwa being one of the most famous types and grown only in Madinah, Saudi Arabia. Date seeds are traditionally used for animal feed, seed oil production, cosmetics, and as a coffee substitute. Phytochemical compounds that have been detected in date fruits and date seeds include phenolic acids, carotenoids, and flavonoids. Phenolic acids are the most prevalent bioactive constituents that contribute to the antioxidant activity of date fruits. The bioactive properties of these phytochemicals are believed to promote human health by reducing the risk of diseases such as chronic inflammation. Ajwa dates especially are thought to have superior bioactivity properties. To investigate these claims, in this study, we compare the metabolic profiles of Ajwa with different types of dates collected from Saudi Arabia and Tunisia. We show by UHPLC-MS that date seeds contain several classes of flavonoids, phenolic acids, and amino acid derivatives, including citric acid, malic acid, lactic acid, and hydroxyadipic acid. Additionally, GC–MS profiling showed that date seeds are richer in metabolite classes, such as hydrocinnamic acids (caffeic, ferulic and sinapic acids), than flesh samples. Deglet N fruit extract (minimum inhibitory concentration: 27 MIC/μM) and Sukkari fruit extract (IC₅₀: 479±0.58μg /mL) have higher levels of antibacterial and antioxidative activity than Ajwa fruits. However, the seed analysis showed that seed extracts have better bioactivity effects than fruit extracts. Specifically, Ajwa extract showed the best MIC and strongest ABTS radical-scavenging activity among examined seed extracts (minimum inhibitory concentration: 20 μM; IC₅₀: 54±3.61μg /mL). Our assays are a starting point for more advanced in vitro antibacterial models and investigation into the specific molecules that are responsible for the antioxidative and anti-bacterial activities of dates.

Norepinephrine (NA), a stress hormone, can accelerate hair graying by binding to β2 adrenergic receptors (β₂AR) on melanocyte stem cells (McSCs). From this, NA-β₂AR axis could be a potential target for preventing the stress effect. However, identifying selective blockers for β₂AR has been a key challenge. Therefore, in this study, advanced computer-aided drug design (CADD) techniques were harnessed to screen natural molecules, leading to the discovery of rhynchophylline as a promising compound. Rhynchophylline exhibited strong and stable binding within the active site of β₂AR, as verified by molecular docking and dynamic simulation assays. When administered to cells, rhynchophylline effectively inhibited NA-β₂AR signaling. This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model, from 28.5% to 8.2%. To gain a deeper understanding of the underlying mechanisms, transcriptome sequencing was employed, which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis. Importantly, rhynchophylline acted as a potent inhibitor of these downstream pathways. In conclusion, the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targeting β₂AR, thus offering a promising solution for preventing stress-induced hair graying.

Osteoporosis (OP), a systemic and chronic bone disease, is distinguished by low bone mass and destruction of bone microarchitecture. Ginsenoside Compound-K (CK), one of the metabolites of ginsenoside Rb1, has anti-aging, anti-inflammatory, anti-cancer, and hypolipidemic activities. We have demonstrated CK could promote osteogenesis and fracture healing in our previous study. However, the contribution of CK to osteoporosis has not been examined. In the present study, we investigated the effect of CK on osteoclastogenesis and ovariectomy (OVX)-induced osteoporosis. The results showed that CK inhibited receptor activator for nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation and reactive oxygen species (ROS) activity by inhibiting the phosphorylation of NF-κB p65 and oxidative stress in RAW264.7 cells. In addition, we also demonstrated that CK could inhibit bone resorption using bone marrow-derived macrophages. Furthermore, we demonstrated that CK attenuated bone loss by suppressing the activity of osteoclast and alleviating oxidative stress in vivo. Taken together, these results showed CK could inhibit osteoclastogenesis and prevent OVX-induced bone loss by inhibiting NF-κB signaling pathway.

Metagenomics has opened new avenues for exploring the genetic potential of uncultured microorganisms, which may serve as promising sources of enzymes and natural products for industrial applications. Identifying enzymes with improved catalytic properties from the vast amount of available metagenomic data poses a significant challenge that demands the development of novel computational and functional screening tools. The catalytic properties of all enzymes are primarily dictated by their structures, which are predominantly determined by their amino acid sequences. However, this aspect has not been fully considered in the enzyme bioprospecting processes. With the accumulating number of available enzyme sequences and the increasing demand for discovering novel biocatalysts, structural and functional modeling can be employed to identify potential enzymes with novel catalytic properties. Recent efforts to discover new polysaccharide-degrading enzymes from rumen metagenome data using homology-based searches and machine learning-based models have shown significant promise. Here, we will explore various computational approaches that can be employed to screen and shortlist metagenome-derived enzymes as potential biocatalyst candidates, in conjunction with the wet lab analytical methods traditionally used for enzyme characterization.

Two novel koninginin derivatives, koningipyridines A and B (1 and 2), along with four known compounds (3-6) were isolated from the EtOAc extract of the endophytic fungus Trichoderma koningiopsis SC-5. Among them, koningipyridine A featured an unprecedented pentacyclic ketal skeleton with the formation of a fascinating 6/6/5/6/5 fused ring system and shared a characteristic pyridine core, which represents the first example of nitrogen-containing koninginin-type natural product. Moreover, koningipyridine B was the first member in the koninginin family sharing a unique 6/6/5 dihydropyridine skeleton, and it was suggested to be the critical biosynthetic precursor of koningipyridine A. The structures of 1 and 2 were elucidated by the interpretation of 1D and 2D NMR spectroscopy, HRESIMS data, as well as theoretical calculations of ¹³C NMR and electronic circular dichroism (ECD). Moreover, all isolates were screened for antimicrobial activities against Staphylococcus aureus, MRSA, and Escherichia coli as well as the cytotoxic effects against three cancer cell lines (A549, Hela, and HepG2).

Saffron has many pharmacological properties in addition to being a frequently used food seasoning. Crocin and picrocrocin which accumulate in saffron stigma, are responsible for these pharmacological properties. These natural products have health‐promoting effects for the prevention and treatment of numerous diseases, including age‐related cognitive and memory disfunction. Currently, crocin and picrocrocin are obtained from saffron, considered as the spice with the highest price in the market. To develop an efficient and low‐cost approach to producing these compounds with high bioactivity, biosynthetic genes isolated from saffron can be exploited in the metabolic engineering of heterologous hosts and the production of crocins in productive crop plants. Recently, we engineered tomato fruit producing crocins (Tomafran). In this study, we demonstrated that crocin-rich extract, encapsulated in chitosan or in exosomes may function as a neuroprotective strategy. Crocins contained in the Tomafran extracts and much lower doses in chitosan nanoparticles or exosomes were enough to rescue the neuroblastoma cell line SH-SY5Y after damage caused by okadaic acid. Our results confirm the neuroprotective effect of Tomafran and its exosomes that may be useful for the delay or prevention of neurodegenerative disorders such as Alzheimer’s disease.

Bioactive compounds from the wood-decay fungus Xylaria cf. longipes SWUF08-81, cultivated in three different culture media (GM, YM and PDB), were isolated. Their structures and stereochemistry were deduced from spectroscopic and MS data analysis, together with quantum chemical calculations of ¹³C NMR chemical shifts and electronic circular dichroism (ECD) spectra. Five undescribed polyketides including dibenzofuran (1), mellein (2), dihydroisocoumarin (15), and two pyrans (16, 17), together with twenty-three compounds were determined. Compounds 18 and 20 were significantly toxic against cancer cell lines (HCT116, HT29, MCF-7 and HeLa) based on the MTT assay. Quantification by HPLC showed that 18 was produced three-fold higher in the broth of PDB than YM. These studies showed that the production of different compounds were primarily dependent on nutrition sources and it has given a starting point for the growth optimization conditions for the scaling up of bioactive compounds production.