Acylated flavonoids are widely distributed natural dietary bioactives with several health attributes. A large diversity of acylated flavonoids with interesting biological potentialities were reported. Of these, 123 compounds with potential antimicrobial, antiparasitic, anti-inflammatory, anti-nociceptive, analgesic and anti-complementary effects were selected from several databases. Based upon these data, the possible mechanistic evidence for their effects were reported. Generally, aromatic acyls i.e., galloyl derivatives appeared to improve efficacy through enhancement of the binding affinities to molecular targets due to plenty of donating and accepting centers. Docking simulations conducted by Molecular Operating Environment (MOE) of acylated flavonoids revealed that compound 12 is at the top of the list into the antibacterial target DNA gyrase subunit B (GyrB), from E. coli, followed by compounds 10, 4 and 23. Compounds 81, 88, 96, 92, 99, 100, 102 and 103 have the strongest binding affinities into Human matrix metallopeptidase (MMP) 2 and 9 catalytic domains. Compound 103 exerted the most balanced predicted dual MMP-2/MMP-9 inhibition action. Compound 95 recorded the strongest binding affinity into metabotropic glutamate receptor (mglur1) with the lowest energy conformer. The data presented in this review suggests that these candidate acylated flavonoids ought to be considered in future drug developments especially as anti-inflammatory and antimicrobial agents.

The Duchesnea genus (Rosaceae) is widely distributed throughout the world, and it is comprised of Duchesnea indica (D. indica) and Duchesnea chrysantha (D. chrysantha) species excluding varieties. The whole plant of Duchesnea genus has been used as a folk medicine for almost 2000 years in Asia. Its phytochemicals mainly include phenolic acids and their derivatives, flavonoids, terpenoids, tannins, lignins, sterols, among others. Modern pharmacological studies have shown that the Duchesnea genus exhibits a wide range of pharmacological effects, such as anticancer, antioxidant, anti-inflammatory, antiviral, antimicrobial activities, and so on. Nowadays, Duchesnea genus is mainly used in the treatment of various malignant tumors. However, its pharmacological activity research is mainly focused on plant extracts, while the pharmacological activities of its pure compounds, their mechanisms of action are seldom studied. Simultaneously, there is limited research on the synergistic effects of multiple effective parts, multiple components, and multiple targets. Additionally, there are few proprietary drugs mainly based on the Duchesnea genus, and their toxicity remains ambiguous. This review provides an overview of the phytochemical and pharmacological investigations of Duchesnea genus, and the applications of multi-target affinity ultrafiltration are prospected, aiming at providing further comprehensive information about the active compounds from Duchesnea genus for drug discovery and development. Synoptically, it is imperative and significant to clarify their toxicity, develop clinical preparations based on Duchesnea genus plants as a single drug or active ingredient, and strengthen the research on the synergistic effects of their multiple components, multiple targets, and multiple effective parts.

In cereals and legumes, phytic acid (PA) is the principal phosphorus reserve that serves the biosynthetic and nutritional demands of growing tissues during germination. Because of strong antioxidant activity and ability to chelate mineral ions, it provides several health and physiological benefits. Phytic acid is widely regarded as an anti-nutritional factor as it can bind minerals and proteins, thus decreasing their bioavailability. However, its chelating property is likely to provide several health benefits, including lowering the risk of diabetes and some malignancies, improving heart health and checking kidney stone formation. Furthermore, recent research has revealed that PA is effective against foodborne bacteria. These beneficial properties of PA open up the possibility of value-added applications in several new areas. Due to its various proven properties, PA has drawn more attention as an anti-nutrient than a beneficial compound. Nevertheless, the available food processing techniques for raw material preparation can be used to reduce the PA concentration in foods to mitigate its anti-nutritional effects. The resulting low PA products may find newer applications in the food industry. This paper aims to provide a general overview of phosphorus transport to different plant organs, biosynthesis of PA and its beneficial and anti-nutritional effects and a description of dephytinization methods.Graphical abstract

Psoriasis is an autoimmune, chronic skin disorder with complex and yet unclear pathogenesis. It is associated with many conditions, including psoriatic arthritis, cardiometabolic syndrome, and depression, leading to a significant reduction in patients’ quality of life. Currently, there is no established procedure to cure psoriasis, but only to control psoriasis symptoms and reduce psoriasis-related comorbidities. Research over the past decades is demonstrating a shift in the treatment framework of psoriasis and development of tailored treatment regimes in order to meet patient’s specific needs based on treatment goals, disease severity, presence of comorbidities, response to previuos therapies, impact on quality of life, and reduction of health risks. Plants and plant-derived molecules have gained considerable interest as possible alternatives of current psoriasis treatments due to their multi-target benefits and fewer side effects compared to synthetic drugs. Natural products from herbal medicines have synergistic effects in alleviating psoriasis and its comorbidities because of their structural diversity and multiple active mechanisms. The potential of plant-derived molecules to regulate the balance between T regulatory (Treg) and T helper 17 (Th17) cells, the processes of cell proliferation and differentiation, and to control inflammation and oxidative stress have attracted more attention in basic and clinical studies. In this review, the balancing and regulating mechanisms that modulate some important signaling pathways involved in psoriasis are discussed and explained.Graphical abstract

Saccharides play a vital role in the human diet due to their beneficial biological and functional properties. The adverse limitations of conventional extraction methods for plant saccharides have led to the search for advanced, ecofriendly, and cost-effective extraction techniques. This review focuses on the five major emerging advanced non-conventional green techniques: ultrasound-assisted, microwave-assisted, enzyme-assisted, supercritical fluid, and pressurized liquid extractions. The review briefly describes the extraction principle and mechanism, advantages and limitations, and the influential operating parameters for each technique. In addition, recent trends and progress in these advanced extraction methods are discussed with a critical comparison of these techniques. Furthermore, the various process modifications and integration aspects of extraction techniques are scientifically commented upon. Challenges and future research prospects for these emerging green technologies for lignocellulosic biomass extraction are also pointed out, emphasizing the industrial realization of these techniques.Graphical abstract

Plant growth and resilience require balancing an inherently oxidative metabolism with powerful antioxidant systems that help maintain homeostasis. When the environment changes, reactive oxygen species are potent indicators of that change, allowing adaptation through re-balancing metabolism and antioxidant systems. A large body of evidence supports the use of exogenously applied antioxidants to improve both plant growth and their resilience to stress. Notably, some phenotypic effects are similar upon the application of chemically diverse antioxidants, while others are distinct. In this review, we analyze research from antioxidant treatment experiments and highlight the similarities in their practical applications and their effects on plant stress tolerance, photosynthesis, native antioxidant systems, and phytohormones. We also briefly cover the specific effects of individually applied antioxidants and what is known about their potential modes of action. Given the strong potential of antioxidant applications, we discuss research needed to promote their agricultural use. Finally, we identify outstanding questions about how the exogenous application of antioxidants mechanistically affects plant growth.

Dendrobium nobile Lindl (DNL) is one of the main sources of traditional Chinese medicine, Shihu (Dendrobii caulis). In recent years, the strong antitumor activity of the extract from DNL makes it a hot research object. This paper systematically summarizes the researches of DNL from 1935 to 2022, including the botanical characteristics, herbal textual research, chemical composition, pharmacological activity and toxicology of DNL, in order to provide inspiration for the later research, further development, as well as reasonable application of DNL. The stems of DNL contains alkaloids, polysaccharides, sesquiterpenes, Phenanthrenes, benzenes and other chemical components. Among them, alkaloids and polysaccharides have been regarded as the main active constitutents, with dendrobine (1) the characteristic components. So far, as many as 213 compounds have been isolated from DNL, and 101 compounds have been identified from the flowers of DNL via gas chromatography-mass spectrometry (GC–MS). It has been found that the extract of DNL exhibit various pharmacological activities, such as anti-tumor, blood sugar reduction, nerve protection, immuneenhancement, anti-inflammation, and anti-aging. Most of the pharmacological researches are on the total polysaccharides and total alkaloids of DNL. Besides being used as a medicinal material, DNL also often appears in daily diet and health care. However, the toxicity of DNL was reported in some literatures. Therefore, more in-depth toxicological research is needed to ensure the safety of DNL in medicine and food consumption.Graphical abstract

Strigolactones (SLs) are a unique and novel class of phytohormones that regulate numerous processes of growth and development in plants. Besides their endogenous functions as hormones, SLs are exuded by plant roots to stimulate critical interactions with symbiotic fungi but can also be exploited by parasitic plants to trigger their seed germination. In the past decade, since their discovery as phytohormones, rapid progress has been made in understanding the SL biosynthesis and signaling pathway. Of particular interest are the diversification of natural SLs and their exact mode of perception, selectivity, and hydrolysis by their dedicated receptors in plants. Here we provide an overview of the emerging field of SL perception with a focus on the diversity of canonical, non-canonical, and synthetic SL probes. Moreover, this review offers useful structural insights into SL perception, the precise molecular adaptations that define receptor-ligand specificities, and the mechanisms of SL hydrolysis and its attenuation by downstream signaling components.

Marine algal-derived endophytic fungi (MAEF) have proven to be unabated sources of novel secondary metabolites with remarkable scaffold diversity, structural complexity, and significant bioactivity. The growing trend in the discovery of new secondary metabolites from MAEF has continued increasing over the last few years. Our previous review summarized a total of 182 secondary metabolites isolated from MAEF covering from 2002 to mid-2015. To update the latest studies of intriguing secondary metabolites of MAEF, this present review covered 196 newly-discovered metabolites of MAEF from the beginning of 2016 to the end of 2021, which were categorized into terpenes and steroids (including bisabolane-type sesquiterpenes, cyclonerane-type sesquiterpenes, diterpenes, sesterterpenes, meroterpenoids, and steroids), nitrogenated compounds (including diketopiperazines, peptides, and other N-containing compounds), polyketides (including azaphilones, tetramic acid derivatives, chromenes, and chromone derivatives), phenolic compounds, and carboxylic acids derivatives based on their putative biogenetic origins. Crucial insights into their chemical diversity and biological activities are provided herein.

New therapeutic agents for amoebic keratitis are needed considering that drugs currently marketed are toxic and not effective against protozoan cystic forms. The antimicrobial action of essential oils (EOs) is already reported in the literature, which has motivated investigations of their anti-Acanthamoeba potential. Unlike synthetic drugs, plant materials have been often identified as less cytotoxic. In this review, the anti-Acanthamoeba potential of EOs was demonstrated not only based on the anti-protozoan activity as anti-inflammatory activity. Finally, in vitro cytotoxicity studies of EOs active were analyzed. EOs were able to prevent the conversion of the protozoan trophozoite to cystic form. In a study performed with Trachyspermum ammi EO, 100% of Acanthamoeba cysts were eliminated. Thymus capitatus and Limonium oleifolium EOs showed to be more active against Acanthamoeba, presenting IC50 values close to chlorhexidine and lower than amphotericin B. For these two OEs, low in vitro cytotoxicity was also found, which result in a high selectivity index (SI > 10). Therefore, safer and more effective therapies could be achieved with OEs, and in vivo assays should be urgently performed to confirm these benefits. Graphical abstract

The species Caesalpinia s.l. (Leguminosae: Caesalpinioideae) are widely distributed over all continents and content a large amount of unusual secondary metabolites with vast biological potential. Traditionally, this genus includes more than 150 species, but currently, in an attempt to group the species by similar phylogenetic characteristics, Caesalpinia s.l. was categorized into the following nine different genera: Caesalpinia s.s., Coulteria, Erythrostemon, Guilandina, Libidibia, Mezoneuron, Poincianella, Pomaria and Tara. Recently, some taxonomic groups were relocated to genera from the informal Caesalpinia Group, such as Cenostigma, Moullava, Biancaea and Hultholia. However, pharmacological and chemical studies continue to use the original genera in their research. Eight hundred thirty-one compounds, including 479 new occurrences in natural products, have been identified and described in the literature in the last decade. Despite the large number of studies, the main species remain scientifically unexplored. Of the more than 140 species belonging to the segregated genera, only 30 species were analysed in chemical studies, all of which are described in this work. A review of the taxonomy of the genus Caesalpinia s.l. revealed that the reclassification, which led to the union of species based on morphological characteristics related to chemical composition, divided species with unusual chemical constituents into distinct genera. In addition, this revision reflects on the taxonomic reclassification of the genus to update the scenario of structures already isolated in the genera and the biological and pharmacological properties of constituents obtained from Caesalpinia and the other segregated genera, considering an updated nomenclature and a previous reclassification covering the available data in the literature published from 2010 to 2022.

Several climatic trends are generally associated with altitude, that may influence the nutritional and phytochemical composition of plants. Strawberry is considered a functional food due to biological activities and health benefits. This systematic review and meta-analysis intend to expose possible variations on physicochemical composition and antioxidant capacity of strawberries in regard to altitude. Thirty eligible studies were included for the final meta-analysis. Two altitude ranges were established: 0 – 1000 and 1000—2000 m above sea level. A random-effects model was used to obtain the results. It was discovered that total soluble solids significantly decreased with altitude. Total titratable acidity increased with altitude. Vitamin C and total anthocyanins showed a significant difference between the groups before we discarded some studies. The analysis of altitude for phenolics and antioxidant capacity evaluated for the DPPH radical scavenging method did not identify any significant differences between the studies. The findings suggest that altitude does not affect the physicochemical composition and antioxidant capacity of strawberries; nonetheless, a more exhaustive study is recommended.Graphical abstract

β-Elemene is a valuable sesquiterpene isolated from the essential oil of the traditional Chinese medicine Curcuma wenyujin. As a Chinese class II non-cytotoxic antitumor drug, β-elemene has been broadly used to treat various cancers due to its excellent anti-tumor activity, inhibition of tumor cell migration, and relatively minor adverse effects. Commercial β-elemene is mainly produced via extraction from traditional Chinese medicinal plants and by chemical synthesis. However, limitations in medicinal plant resources and the complexity of chemical synthesis restrict its use given the growing demands. Therefore, it is imperative to identify high-yield biological sources, improve production strategies, develop effective downstream processing, and evaluate the therapeutic applications of β-elemene. Several studies have thoroughly elucidated pathways of β-elemene synthesis in plants and heterologous biosynthesis in microorganisms, which may provide a promising alternative approach for industrial production. The current review aims to discuss the β-elemene biosynthetic pathways and key enzymes involved. Since β-elemene exhibits sensitization properties, and anti-inflammatory and antioxidant effects, recent progress in the understanding of its molecular mechanisms and toxicity, and the application prospects of β-elemene as a medicine have also been critically reviewed here.

Terpene synthases catalyze the first committed step in the biosynthesis of terpenes, a structurally diverse class of natural products that also encompasses volatiles derived from precursors in the C10 to C15 range (termed monoterpenes and sesquiterpenes, respectively). In the review section of this article, we are providing information about all functionally characterized monoterpene synthases (MTSs) and sesquiterpene synthases (STSs) of Cannabis sativa L. We are also exploring the locations of MTSs and STSs in the chromosome-level assembly of the reference chemovar CBDRx. A follow-up computational structure–function analysis focuses on MTSs, as there is already a rich literature available on the topic. More specifically, by employing sequence comparisons and homology structural modeling, we infer which amino acid residues are likely to constrain the available space in the active site of cannabis MTSs. The emphasis of these studies was to investigate why some MTSs accept only a C10 diphosphate as substrate, while mixed MTS/STS enzymes also accommodate a C15 diphosphate. By combining a literature review and computational analyses in a hybrid format, we are laying the foundation for future studies to better understand the determinants of substrate and product specificity in these fascinating enzymes.

Chronic kidney disease is a syndrome defined as the continuous change of renal structure, considered as one of the top 10 causes of death worldwide. In the past few decades, dietary flavonoids and their derivatives have been proved as potential drugs to control chronic kidney disease. There also seems to be a relationship between the intake of dietary flavonoids and nephropathy incidence. This study reviews the metabolism and bioavailability of plant flavonoids with different structures and their multifunctional role in inhibiting chronic kidney disease. The alleviating effect of plant flavonoids in chronic kidney disease is attributed to several mechanisms, including reduction of oxidative stress, immune modulation anti-inflammation, renal fibrosis inhibition, anti-apoptosis, and regulating gut flora. It also discussed how plant flavonoids regulate the intestinal flora of chronic kidney disease patients and further improve renal health through the gut-kidney axis. In addition, the products and development prospect of plant flavonoids are also introduced.Graphical abstractThe main sources of flavonoids and their related mechanisms in the treatment of chronic kidney disease

Brazilian arnicas belong to the Asteraceae family and can be mainly found in the Brazilian biome Cerrado (savanna) but also Caatinga, Atlantic Forest, Pampa, Pantanal, and Amazonia Forest. The plant’s leaves, roots, inflorescences, and flowers have demonstrated high medicinal potential use as evidenced by recent studies. The Brazilian arnica species were selected based on their ethnopharmacological representativeness, with the 9 most relevant species being identified: Calea uniflora Less, Chaptalia nutans (L.) Polák., Lychnophora ericoides Mart, L. pinaster Mart. and L. salicifolia Mart, Porophyllum ruderale (Jacq.) Cass., Pseudobrickellia brasiliensis (Spreng.) R.M. King & H. Rob. Solidago chilensis Meyen, Sphagneticola trilobata (L.) Pruski. Brazilian arnicas species have many pharmacological/bioactive constituents such as flavonoids, phenolic compounds, and terpenoids, especially monoterpenes, and sesquiterpenes. Experimental in vitro and in vivo studies indicate its benefits to prevent, improve and treat human conditions or diseases with several beneficial effects such as anti-inflammatory, analgesic, antiedematogenic, antimicrobial, antioxidant, trypanocidal, and leishmanicidal activity. Arnicas extracts and their bioactive compounds have been suggested as useful tools in the industry, for example, in topical formulations and green chemistry. Like many other native plants spread throughout Brazil, arnicas have a high functional potential that needs further exploration. In this context, the present review aims to describe the potential use of Brazilian arnicas, highlighting their geographic distribution, uses in traditional medicine, bioactive composition, health effects, and potential applications.Graphical abstract

The common medlar (Mespilus germanica L.) is one of two species within the Mespilus genus (Maloideae subfamily). Its use can be traced back almost 30 centuries, from ancient Assyrians and Babylonians to Greeks and Romans and through modern times. During the Middle Ages it was a popular fruit tree and a highly appreciated ornamental tree in gardens across Europe. However, in modern times, the medlar is often considered an underestimated and underutilized fruit from the Rosaceae family. Nevertheless, it is slowly regaining its ‘medieval glory’ and commercial importance as a food-stuff for human consumption. The medlar plant has a wide array of traditional uses in both gastronomy and medicine. Ripe medlar fruits can be consumed fresh or processed into different products such as juice, concentrate, jam, cheese, leather, and honey. Meanwhile, unripe fruits can be used to prepare pickles or beverages such as cider. The nutritional potential of medlar fruits is attributed to sugars, organic acids, fatty acids, carotenoids, amino acids and proteins, vitamins, and essential elements. Scarce literature describes the richness of medlar fruit in bioactive phenolic compounds such as flavonoids and phenolic acids, which contribute to its antioxidant and antidiabetic properties. Additionally, a few studies describe other biological properties of the medlar plant including antimicrobial, cytotoxic and neurodegenerative effects of medlar fruits and leaves, while reports on the clinical studies are lacking. This review paper summarizes the chemical and nutritional properties of medlar fruit, traditional medicinal uses and biological activity of the medlar plant, relying on the most relevant and up to date scientific literature in the field.Graphical abstract

In recent decades, the therapeutic potential of cannabinoids and analogous compounds has been intensively investigated. The endocannabinoid system has already been identified in the skin and, although much remains to be discovered about its contribution and importance for the maintenance of skin homeostasis, it has been increasingly associated as promising for dermatological disorders’ management. Cannabidiol (CBD), the main non-intoxicating phytocannabinoid in cannabis, has been shown to have hydrating, sebostatic, antipruritic, antimicrobial, anti-inflammatory, antioxidant, wound healing, photoprotective, anti-fibrotic and antitumoral, as well as modulating hair growth. Thus, CBD has gained attention concerning its application in cutaneous pathologies such as atopic dermatitis, psoriasis, acne, epidermolysis bullosa, systemic sclerosis, seborrheic dermatitis, androgenetic alopecia and cutaneous melanoma, although its bioactivities still lack scientific evidence and some of its mechanisms of action remain to be elucidated. Given its physicochemical characteristics, its topical administration becomes challenging, and it is necessary to develop new technological strategies to overcome the skin intact barrier. This review describes the latest evidence that exists on the application of CBD to the skin, the problems inherent to its chemical structure and that compromise its cutaneous administration, and the different strategies and formulations that have been studied to improve it, also clarifying some CBD-containing cosmetics products that are already available on the market. Graphical Abstract

The large family of cytochrome P450 enzymes are heme containing proteins generally associated with the cytoplasmic face of the endoplasmic reticulum in Eukaryotic cells. They play essential roles in detoxification mechanisms of cellular processes and are key components in biosynthesis and evolution of specialized metabolites having various biological activities in the plant kingdom. The assembly of complex monoterpenoid indole alkaloids and benzylisoquinoline alkaloids involves numerous cytochrome P450 enzymes that participate in their chemical diversification and that act as central scaffolds for recruitment of the biosynthetic enzymes required for their production. The present review discusses the roles played by different CYP families (-71, -72, -75, -76, 80-, 82-, -86 and -719) in the diversification of MIA and BIA pathways that have been discovered and characterized. Recent studies using homology model guided site-directed mutagenesis coupled with determination of biochemical function are described that provide insights about how small modifications in protein structures allowed the evolution of new substrate specificity and the appearance of new monoterpenoid indole alkaloids and benzylisoquinoline alkaloids in Nature.