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On the basis of a streamlined route to the pyrroloiminoquinone (PIQ) core, we made 16 natural products spread across four classes of biosynthetically related alkaloid natural products, and multiple structural analogs, all in ≤8 steps longest linear sequence (LLS). The strategy features a Larock indole synthesis as the key operation in a five-step synthesis of a key methoxy-PIQ intermediate. Critically, this compound was readily diverged via selective methylation of either (or both) of the imine-like or pyrrole nitrogens, which then permitted further divergence by either O-demethylation to o-quinone natural products or displacement of the methoxy group with a range of amine nucleophiles. Based on a single, early report of their potential utility against the malaria parasite, we assayed these compounds against several strains of Plasmodium falciparum, as well as two species of the related protozoan parasite Babesia. In combination with evaluations of their human cytotoxicity, we identified several compounds with potent (low-nM IC50) antimalarial and antibabesial activities that are much less toxic toward mammalian cells and are therefore promising lead compounds for antiprotozoal drug discovery.

Zanthoxylum nitidum is a traditional Chinese herb, but limited information is available concerning its antioxidant activity of Z. nitidum. In this study, the bioactive components, content, and antioxidant activity of Z. nitidum roots from various regions in southern China were detected and evaluated. The results revealed that the highest nitidine chloride content found in S13. The S1 contained significantly higher concentrations of hesperidin, total flavonoids, and total phenols than other samples. The samples from S13, S1, and S12 had the strongest comprehensive antioxidant activity. Stoichiometric analysis revealed that samples from various regions were effectively identified and classified. This is the first study to investigate the antioxidant activity of wild-type Z. nitidum in southern China. It lays the groundwork for Z. nitidum harvesting, origin identification, sensible use, as well as the quality evaluation of Z. nitidum resources, particularly in vitro antioxidant activity assessment. [ABSTRACT FROM AUTHOR]

The new natural products reported in 2023 in peer-reviewed articles in journals with good reputations were reviewed and analyzed. The advances made by Asian research groups in the field of natural products chemistry in 2023 were summarized. Compounds with unique structural features and/or promising bioactivities originating from Asian natural sources were discussed based on their structural classification. [ABSTRACT FROM AUTHOR]

Background: The simplest form of carbohydrate that the human body can utilize efficiently to fuel various functions in our body is glucose. The food that is consumed by us in any form is acted upon by pancreatic juices, bile, and several other digestive enzymes and is converted into its simplest form, which is absorbed by the small intestine and is diffused into the circulatory system; from there, it is transported to other organs via GLUT-2 and GLUT-4 transporters. This process is very important, and so are the hormones involved in it. One such major hormone responsible for glucose homeostasis in the body is insulin. Its malfunction or that of either of its signaling components leads to a metabolic disorder termed "diabetes." Hyperglycemia is a grave condition associated with this complex disease and is of global concern. The impact of this disease can be life threatening if adequate precaution, medication, and therapy are overlooked. A plethora of synthetic drugs are available in the market, and the main goals of these antidiabetic medicines are to improve insulin sensitivity and/or production as well as to lower blood glucose levels. In all cases, frequent use of antidiabetic medication causes several after-effects. Results: Numerous studies in this field demonstrate that antidiabetic phytomolecules are highly effective against diabetes patients and are almost completely without side effects. Almost all classes of phytomolecules have been thoroughly evaluated to develop the noble plant-based drug. Conclusion: The current review discusses diabetes, its classification and management, worldwide occurrence, and the most crucial class of antidiabetic phytomolecules, for example, alkaloids, and terpenenoids as well as the parent molecule responsible for the bioactivity, subclasses, their mechanisms of action, plant sources and part, their superiority over synthetic drug, and new advances in this area. [ABSTRACT FROM AUTHOR]

Aconiti Lateralis Radix praeparata (also known as Fuzi in Chinese) has been extensively used in clinic. However, the toxicity issues limit the therapeutic range of Fuzi. Thus, a rapid and sensitive HPLC‐MS/MS method was developed to simultaneously quantify and compare six active/toxic constituents in decocting extracts from four different processed Fuzi products and in rat plasma after oral administration of its decocting extracts. The selectivity, linearity, sensitivity, precisions, accuracy, matrix effects, extraction recoveries, and stability were validated. The comparative analysis of six alkaloids in decocting extracts between the four kinds of Fuzi products were conducted by the validated HPLC‐MS/MS. Principal component analysis (PCA) and orthogonal partial least‐squares discriminate analysis (OPLS‐DA) were adopted to compare the differences of decocting extracts from the different processed Fuzi products. Besides, selecting Heishunpian (HSP) as the representative of the processed Fuzi products, we investigated the pharmacokinetic behaviors of these major alkaloids after oral administration. The developed HPLC‐MS/MS method to simultaneously analyze these aconitine‐type alkaloids in decocting extracts, and its pharmacokinetic behavior after oral administration may pave a way for quality control of Fuzi and monitoring the safety and rationality of clinical prescriptions. [ABSTRACT FROM AUTHOR]

Corn silk (Stigma maydis) is one of the traditional medicines for treating many microbial infections. However, there is little literature on the bioactive compounds responsible for these activities. This study was designed to investigate the phytochemical constituents present in corn silk and to screen the isolated compounds for antimicrobial activity. The pulverized plant sample of 1.14 kg was extracted with 3.6 L of methanol by cold maceration for 3 days. The extract was screened for phytochemicals, followed by isolation of constituent phytochemicals, characterization, and identification of isolated compounds. The isolates were screened for antibacterial and antifungal activities. The phytochemical screening revealed the presence of alkaloids, flavonoids, coumarins, tannins, reducing sugars, saponins, terpenoids, sterols, and cardiac glycosides. Further phytochemical investigation of the chloroformic subfraction of the methanolic extract of the silk led to the isolation of behenic acid and stigmasterol after running column chromatography as well as other chromatographic methods. The identity of the isolated compounds was established based on extensive spectroscopic analyses of their IR, 1D, 2D NMR data and comparing the data to the reported literature. Stigmasterol was active against Staphylococcus aureus and the fungal strain Candida albicans at 25 µg/mL while the mean minimum inhibitory concentration of behenic acid against Staphylococcus aureus was 100 µg/mL, Tinea corporis and Klebsiella pneumoniae were susceptible at 25 µg/mL. The study showed that plant secondary metabolites might be responsible for the reported biological activities of corn silk. It is the first report of behenic acid isolated from corn silk. [ABSTRACT FROM AUTHOR]

The Atlantic coastline of El-Jadida, Morocco, is renowned for its plentiful algae, especially brown seaweed, which is rich in active compounds known for their antifungal properties. This valuable resource offers an exciting opportunity to tackle the numerous challenges posed by invasive fungal infections, allergies, mycotoxin-related food poisoning, and drug-resistant strains. Underscoring the urgent need to explore alternative, sustainable, and environmentally friendly antifungal agents derived from algae. This study aimed to evaluate the antifungal activity of total alkaloids and phenolic-rich fractions derived from seven species of Pheophyceae: Sargassum muticum, Sargassum vulgare, Bifurcaria bifurcata, Cystoseira tamariscifolia, Cystoseira humilis, Laminaria ochroleuca, and Fucus spiralis against four fungi: airborne toxigenic isolates of Aspergillus westerdijkiae and Chaetomium globosum as well as nosocomial opportunistic isolates of Aspergillus nidulans and Scopulariopsis brevicaulis. The study also aimed to identify the most effective alga and its specific active compounds through LC–MS and GC–MS analysis. The invasive Sargassum muticum was chosen as the most potent alga in inhibiting the growth of mycelium. For the first time, the alkaloids palmatine and jatrorrhizine, along with caulerpin, have been identified. The chloroform fraction revealed the prevalence of phenolic compounds including, phenolic acids, flavonoids, and phlorotannins. The lowest minimum inhibitory concentrations (MICs), with a maximum fungal load of 108 colony-forming unit (CFU), recorded ranged from 3.12 to 6.25 μg/mL by the phenolic-rich fraction against airborne toxigenic isolates, and from 100 to 200 μg/mL against nosocomial opportunistic isolates by the total alkaloids. In comparison, the positive control, ketoconazole, showed higher MICs and resistance against A. nidulans. The valorization of Sargassum muticum is proposed as a green strategy to preserve the ecological balance, combat antifungal resistance, and address public health challenges. [ABSTRACT FROM AUTHOR]

ABSTRACT Bangladesh is endowed with an abundance of excellent medicinal plant resources. A well‐known traditional medicinal plant Piper chaba H. from the Piperaceae family is rich in bioactive phytochemicals that have antidiarrheal, antimicrobial, analgesic, antioxidant, anticancer, and cytotoxic effects. This plant is locally known as “Chuijhal,” and the stem is used as spices. In the current research program, the stems of the P. chaba plant were selected and its chemical and biological investigations such as antidiarrheal, antimicrobial, and analgesic effects were performed. Moreover, docking models were accomplished by exploiting PyRx‐Virtual Screening software and implied that isolated compounds of P. chaba exert different pharmacological activity by inhibiting their targeted receptors. Phytochemical investigations revealed the isolation of Chingchengenamide A, a relatively rare alkaloid from the stems of P. chaba. Another alkaloid Chabamide I which is a piperine dimer was also isolated. Their structures were confirmed by comparing these compounds' spectral data (1H and 13C NMR) with their previously published spectral data. Antidiarrheal activity shows a percent reduction of diarrhea by 46.67% and 40%, respectively, for Chabamide I and Chingchengenamide A (at 20 mg/kg b.w.) compared with an 80% reduction by standard loperamide. Similarly, the percent reduction of writhing was 53.06% and 42.86%, respectively, for Chabamide I and Chingchengenamide A at similar doses compared with an 80% reduction by diclofenac sodium considered as standard. Both the alkaloids showed auspicious outcomes against test microorganisms during disk diffusion antimicrobial assay. Molecular docking and ADME/T analysis of the alkaloids also validate a potent pharmacological basis for the traditional utilization of P. chaba in treating diarrhea, pain, and microbial infection. These results emphasize the need to investigate P. chaba as a potential source of natural therapies for common health issues, laying the foundation for future research. [ABSTRACT FROM AUTHOR]

Summary The protein crops known as lupins have been bred to accumulate low levels of antinutritional alkaloids, neglecting their potential as sources of valuable metabolites. Here, we engineered narrow‐leafed lupin (NLL) to accumulate large amounts of a single alkaloid of industrial interest called (−)‐sparteine. While (−)‐sparteine is recognized as a key auxiliary molecule in chiral synthesis, its variable price and limited availability have prevented its large‐scale use. We identified two enzymes that initiate the conversion of (−)‐sparteine to a variety of alkaloids accumulating in NLL. The first one is a cytochrome P450 monooxygenase belonging to family 71 (CYP71D189), and the second one is a short‐chain dehydrogenase/reductase (SDR1). We screened a non‐GMO NLL mutant library and isolated a knockout in CYP71D189. The knockout displayed an altered metabolic profile where (−)‐sparteine accounted for 96% of the alkaloid content in the seeds (GC–MS basis). The (−)‐sparteine isolated from the mutant seeds was enantiomerically pure (99% enantiomeric excess). Apart from the altered alkaloid profile, the mutant did not have any noticeable phenotype. Our work demonstrates that (−)‐sparteine is the precursor of most QAs in NLL and expands the current uses of NLL as a crop. [ABSTRACT FROM AUTHOR]

AbstractTwo new quinazolinone alkaloids, benzomalvin F (1), and quinadoline C (2), along with four known quinazolinones (3-6), were isolated from cultures of the wetland-soil-derived fungus Aspergillus udagawae from the Huixian wetland in Guilin. Their structures were elucidated based on detailed spectroscopic analysis, including 1D, 2D NMR, mass spectrometry, and IR spectra. In addition, the anti-inflammatory results showed that compounds 1, 2, 4, and 5 had significant inhibitory effects on NO production in RAW264.7 cells activated by lipopolysaccharide (LPS), with IC50 values of 24.5 ± 0.1, 29.7 ± 0.1, 29.4 ± 0.1, and 31.0 ± 0.1 µM respectively, compared with the positive control indomethacin (IC50 = 31.6 ± 0.4 μM). [ABSTRACT FROM AUTHOR]

Envenomations by snakes represent a neglected health problem in tropical and subtropical countries. In South America, Lachesis muta occasionally causes severe human envenomation, with treatment being conditioned to an unspecific antivenom. In this work, we examined the neutralizing ability of Coutarea hexandra stem bark hydroalcoholic extract (Ch‐E), including the commercial phytochemicals coumarin and quinine, on the neuromuscular blockade induced by L. m. muta venom in mouse phrenic nerve‐diaphragm preparation. Biological assays were performed following conventional myographic technique ex vivo. Ch‐E was phytochemically characterized to detect the presence of coumarin and quinine using analytical methods. Ch‐E and commercial phytochemicals were tested separately or combined under pre‐ and post‐venom incubation protocols. Ch‐E attenuated the venom‐induced neuromuscular blockade only under the pre‐venom incubation protocol. Quinine was not detected in Ch‐E. Commercial coumarin and quinine exhibited a concentration‐dependent counteracting effect on the venom‐induced neuromuscular blockade. The pre‐venom incubation protocol showed to be efficient in attenuating the L. m. muta venom–induced neuromuscular blockade, most likely due to the presence of coumarin derivatives and unknown alkaloids in this extract. [ABSTRACT FROM AUTHOR]

ABSTRACT Two new alkaloids, named migenomycin I (1) and II (2), along with nine known compounds (3–11), were isolated from the fungus Rhizopus oryzae from Atractylodes macrocephala Koidz. The structures of compounds 1 and 2 were determined by spectroscopic methods (MS, NMR, and CD). All compounds were isolated from Rhizopus oryzae for the first time. In addition, the antitumor activities of compounds 1 and 2 and the hypoglycemic activities of most compounds were evaluated. [ABSTRACT FROM AUTHOR]

The lack of vaccines shows the need for alternative leishmaniasis treatments. In vitro study previously demonstrated the leishmanicidal activity of A. nitidum extracts. This study describes for the first time, the antileishmanial activity of A. nitidum extracts in infected Balb/c mice and its immunomodulatory effect. The extract (EE) was obtained by maceration of the peel powder with ethanol, which was fractionated by acid-base partition, originating the alkaloid (FA) and neutral (FN) fractions. EE and FA were analyzed using mass spectroscopy. Daily intragastric treatment was performed with EE and FA, at doses of 200 mg/kg and 400 mg/kg, in Balb/c mice with 28 days of infection by Leishmania amazonensis. A thickness gauge was used to assess the progression of the lesion and the MTT method to determine the parasite load in the spleen. The quantification of IL-10 and IFN-γ was performed by ELISA. Analysis of the mass spectrum of EE indicated the presence of the alkaloids corynantheol and yohimbine, while in FA the alkaloid dihydrocorynantheol was identified. To elucidate the mode of interaction of these alkaloids with the TR protein, molecular target of antileishmanial drugs, we used molecular modeling approaches such as docking, molecular dynamics simulations and free energy affinity. Treatment with EE for 28 days at the highest dose tested, significantly reduced the size of the lesion. EE and FA after 28 days of treatment showed dose-dependent antileishmanial activity, which reduced the parasite load in the spleen of infected mice by 42.5% and 22.1%, respectively. Both EE and FA presented immunomodulatory effect, as they decreased IL-10 expression and increased IFN-y levels. The effectiveness of A. nitidum in the treatment of cutaneous leishmaniasis was proven in this study. The results obtained in silico demonstrated that the compounds are capable of interacting with the catalytic residues of the TR. The affinity energy results demonstrated that the complexes formed are favorable for enzymatic inhibition. The alkaloids present in the plant have demonstrated not only antileishmanial activity, but also the ability to modulate the host's immune response. These promising results open perspectives for developing more effective and comprehensive treatments against cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Histolocalization and quantification of secondary metabolites established the occurrence of alkaloids, phenols and acetogenins in various plant organs of A. muricata at different stages of plant growth.Annona muricata L. possesses broad assemblage of ethno-pharmaceutical and therapeutic upsides ascribed to biosynthesis of secondary metabolites. Currently, the bioactivity is characterized by the production of acetogenins (ACGs), and also by the biosynthesis of alkaloids, primarily benzylisoquinolines derived from tyrosine and phenolic compounds. As a result of high variability of metabolite production in A. muricata, the present study evaluated the histochemical analysis of various plant parts at different developmental stages of growth. Presences of phytometabolites were determined using in-situ histochemical localization of alkaloids, phenolic compounds and acetogenins, while its estimation employing spectroscopic quantification techniques to understand structure, development, time-course deposition, content and distribution of secondary phytoconstituents. Study revealed distinct presence of secondary metabolites in cells and tissues of all plant organs in various intensities and patterns. Alkaloids and acetogenins occurred mostly in secretory cavities or idioblast cells while sparsely associated with other cells or tissues. Phenolic compounds emerged widely, with no confined distribution patterns occurring in storage cells and tissues. Quantitative analysis revealed highest accumulation of alkaloids, phenols and acetogenins in mature root-barks, mature unripe fruit rind and mature leaf respectively. Secondary metabolites generally occurred in young stages at low concentrations as compared to matured growth stages of plant parts. Such in-situ histochemical and biochemical approach will help in identifying the cells and tissues responsible for synthesis, storage and biological effects of potential secondary metabolites which could be further used for culturing and enhancing its production with biotechnological aids. [ABSTRACT FROM AUTHOR]

Quinine is a historically important natural product containing a methoxy group that has been assumed to be incorporated at a late pathway stage. Here we show that the methoxy group in quinine and related alkaloids is introduced onto the starting substrate tryptamine. Feeding studies definitively show that 5‐methoxytryptamine is utilized as a quinine biosynthetic intermediate in planta. We discover the biosynthetic genes that encode the responsible oxidase and methyltransferase, and we use these genes to reconstitute the early steps of the alkaloid biosynthetic pathway in Nicotiana benthamiana to produce a mixture of methoxylated and non‐methoxylated alkaloid intermediates. Importantly, we show that the co‐occurrence of both tryptamine and 5‐methoxytryptamine substrates, along with the substrate promiscuity of downstream pathway enzymes, enable parallel formation of both methoxylated and non‐methoxylated alkaloids. [ABSTRACT FROM AUTHOR]

Gelsemium elegans Benth alkaloids are the main components of G. elegans and can cause acute toxicosis or even death. Although several studies have reported methods for detecting G. elegans alkaloids, a high-throughput and environmental-friendly strategy for detection of multiple G. elegans alkaloids has not been realized. In this work, a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method was developed for rapid detection of G. elegans alkaloids in human plasma and urine for diagnosis of poisoning. Multiple matrices and crystal spotting methods were evaluated to obtain stable and high peak intensities without "sweet spot". We verified the methodology and obtained excellent results. The matrix effects with different dilutions were compared and good recoveries and a low relative standard deviation were obtained with a 40-fold dilution. This method could shorten the analysis time and greatly reduce the consumption of chemical solvents. Furthermore, it could be applied to quantitative assessment of G. elegans alkaloid poisoning incidents. [ABSTRACT FROM AUTHOR]

ABSTRACT Understanding the molecular signaling pathways of colorectal cancer (CRC) can be accepted as the first step in treatment strategy. Permanent mTOR signaling activation stimulates the CRC process via various biological processes. It supplies the survival of CRC stem cells, tumorigenesis, morbidity, and decreased response to drugs in CRC pathogenesis. Therefore, inhibition of the mTOR signaling by numerous bioactive components may be effective against CRC. The study aims to discuss the therapeutic capacity of various polyphenols, terpenoids, and alkaloids on CRC via the PI3K/Akt/mTOR pathway. The potential molecular effects of bioactive compounds on the mTOR pathway's upstream and downstream targets are examined. Each bioactive component causes various physiological processes, such as triggering free radical production, disruption of mitochondrial membrane potential, cell cycle arrest, inhibition of CRC stem cell migration, and suppression of glycolysis through mTOR signaling inhibition. As a result, carcinogenesis is inhibited by inducing apoptosis and autophagy. However, it should be noted that studies are primarily in vitro dose‐dependent treatment researchers. This study raises awareness about the role of phenolic compounds in treating CRC, contributing to their future use as anticancer agents. These bioactive compounds have the potential to be developed into food supplementation to prevent and treat various cancer types including CRC. This review has the potential to lead to further development of clinical studies. In the future, mTOR inhibition by applying several bioactive agents using advanced drug delivery systems may contribute to CRC treatment with 3D cell culture and in vivo clinical studies. [ABSTRACT FROM AUTHOR]

A concise total synthesis of Cuscutamine was achieved involving a diastereoselective intramolecular acyl iminium ion mediated Pictet‐Spengler reaction. This synthetic strategy provided a direct route to (11S, 13R)‐Cuscutamine (2) in only 3 steps with an overall yield of 56 % and an enantiomeric ratio of 88 %. The diastereoselectivity of the reaction is consistent with previous studies that proceed via more highly puckered transition states and the present results thus reveal the importance of the steric contributions to the observed diastereoselectivity. [ABSTRACT FROM AUTHOR]

The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-β/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of high-quality studies, significant progress will be made in the treatment of fibrosis. [ABSTRACT FROM AUTHOR]

Scientists are becoming alarmed by the rise in drug-resistant bacterial and fungal strains, which makes it more costly, time-consuming, and difficult to create new antimicrobials from unique chemical entities. Chemicals with pharmacological qualities, such as antibacterial and antifungal elements, can be found in plants. Alkaloids are a class of chemical compounds found in nature that mostly consist of basic nitrogen atoms. Biomedical science relies heavily on alkaloid compounds. Based on 241 papers published in peer-reviewed scientific publications within the last ten years (2014–2024), we examined 248 natural or synthesized monomeric alkaloids that have antifungal and antibacterial activity against Gram-positive and Gram-negative microorganisms. Based on their chemical structure, the chosen alkaloids were divided into four groups: polyamine alkaloids, alkaloids with nitrogen in the side chain, alkaloids with nitrogen heterocycles, and pseudoalkaloids. With MIC values of less than 1 µg/mL, compounds 91, 124, 125, 136–138, 163, 164, 191, 193, 195, 205 and 206 shown strong antibacterial activity. However, with MIC values of below 1 µg/mL, compounds 124, 125, 163, 164, 207, and 224 demonstrated strong antifungal activity. Given the rise in antibiotic resistance, these alkaloids are highly significant in regard to their potential to create novel antimicrobial drugs. [ABSTRACT FROM AUTHOR]

The growing interest in vegetable proteins, namely those derived from lupins, has raised concerns over potential safety risks associated with these food products. Lupin serves as the main host for the mycotoxin-producing fungus called Diaporthe toxica. This species, which is associated with animal diseases, has been scarcely characterized. Recently, phomopsin-A (PHO-A), the main mycotoxin produced by D. toxica, was found to be harmful to humans. Therefore, this study aimed at characterizing D. toxica growth and spore formation both in vitro and on lupin samples. In addition, the production of PHO-A and alkaloids was investigated on lupin beans by using three different inoculation methods. Particularly, growth and spore production were evaluated on different media, while PHO-A and alkaloid production were determined by means of µSPE extraction followed by UHPLC-MS/MS and HPLC-MS/MS, respectively. The results have demonstrated differences in growth on different media, with potato and oat-flakes-based media being the best options. Conversely, D. toxica was not able to produce spores on agar media, but only on lupin beans. Moreover, a thorough analysis of PHO-A production revealed an increase over time, reaching values up to 1082.17 ppm after 21 days on artificially rehydrated samples. On the other side, the analysis of alkaloids revealed impressive results, as this species produced great quantities of the quinolizidine alkaloids (QA) that are normally present in lupin seeds such as lupanine, sparteine, multiflorine, and hydroxylupanine. On balance, considering these results, different metabolic pathways were demonstrated in D. toxica, which are not adequately described in the existing literature. These data are of paramount importance to deepen the knowledge about a fungal species that is important to ensure the safety of lupin and lupin-based products. [ABSTRACT FROM AUTHOR]

Bromination by N-bromosuccinimide of the β-carboline alkaloid 8-acetylharmine in CH2Cl2 smoothly formed 8-acetyl-6-bromoharmine. Cross coupling of 8-acetyl-6-bromoharmine with arylboronic acids in aqueous toluene in the presence of Pd(PPh3)4 as a catalyst, Na2CO3 as a base, and ammonium salt Bu4N+Br- as an additive synthesized the corresponding 6-aryl-8-acetylharmine derivatives. The new aryl-substituted 8-acetylharmine derivatives possessed moderate cytotoxicity and antidepressant activity in the Porsolt test. [ABSTRACT FROM AUTHOR]

A paper-based colorimetric sensor array mediated by a novel nanozyme (CuCo2O4) was developed using a screen-printing technology. The aim was to facilitate the identification of different kinds of alkaloids. Typically, three chromogenic substrates (3,3′,5,5′-tetramethylbenzidine, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and o-phenylenediamine) were selected as sensing elements, which can be catalyzed by a CuCo2O4 nanozyme with peroxidase-like activity to yield corresponding oxidized products, thereby inducing color changes. Owing to the varying inhibitory ability of different alkaloids on acetylcholinesterase (AChE), a decrease in choline (Ch) concentration occurs and subsequently results in the restoration of color within the units of sensor array. Color data can be transformed into hue information with a smartphone. The above color variations generated a unique "fingerprint" pattern on five alkaloids (berberine, palmatine, jatrorrhizine, eserine, and harmane), which can be successfully discriminated through linear discriminant analysis in the range 0.2 to 20 µM. Furthermore, the sensor arrays allowed successful discrimination of the above five alkaloids in Chinese herbal medicine samples and recognition of 22 blind samples. This work presents a novel nanozyme-based paper sensor array, which is a user-friendly and reliable platform for probing different alkaloids. In addition, the developed sensing strategy enables the identification of AChE-related diseases, positively contributing to the screening available of AD-associated drugs. [ABSTRACT FROM AUTHOR]

Seven new alkaloids [1, (±)-2, (±)-3, 4, and 5] and one new natural product (6), along with eight known analogues, were isolated from the tubers of Pinellia pedatisecta Schott. Their structures were determined by a comprehensive analysis of spectroscopic data, including HRESIMS, and electronic circular dichroism (ECD). In addition, the results of the bioactivity evaluation showed that compounds (±)-3, 6, and 9 exhibited significantly protective effects against Aβ25-35-induced PC-12 cell injury and ameliorated cell viabilities by decreasing the levels of the reactive oxidative species (ROS) and mitochondrial membrane potential (MMP). [ABSTRACT FROM AUTHOR]

Cancer is one of the most common causes of death in the world. Despite the fact that there are many types of therapies available, cancer treatment remains a major challenge. The main reason for the ineffectiveness of chemotherapy is the acquisition of multidrug resistance (MDR) by cancer cells. One of the factors responsible for the acquisition of MDR is the NRF2 transcription factor, which regulates the expression of proteins such as HO-1, NQO1, MRP1, MRP2, and GST. In normal cells, NRF2 is the first line of defense against oxidative stress, thereby preventing carcinogenesis. Still, its hyperactivation in cancer cells causes them to acquire MDR, which significantly reduces or eliminates the effectiveness of chemotherapy. Considering the important role NRF2 plays in the acquisition of MDR, its modulators and, above all, inhibitors are being sought after, including among compounds of plant origin. NRF2 inhibition may prove to be a key element of anticancer therapy. This review summarizes the current state of knowledge about plant NRF2 inhibitors and presents the effects of their use in overcoming MDR in cancer. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary artery hypertension (PAH) is a devastating syndrome. Our previous studies showed that perillyl alcohol (P), berberine (B) and quercetin (Q) improve PAH. In this study, we investigated the effects of sub-effective doses of these derivatives in double and triple combination forms on PAH in rats. Materials and Methods: Forty nine rats were divided into seven groups (n=7): 1) control, 2) monocrotaline (MCT), 3) MCT+vehicle (veh), 4) MCT+BP, 5) MCT+PQ, 6) MCT+BQ, and 7) MCT+BPQ. After three weeks of PAH induction with MCT (60 mg/kg), either vehicle (ethanol 5% in saline) or one of the above combinations (dose of 20 mg/kg for B, and doses of 20 and 10 mg/ kg for P and Q in vehicle) was administered for three weeks. Right ventricular (RV) pressure, contractility indices, lung pathology, miR-204 expression, oxidative stress markers, inflammation and apoptosis were assayed. Results: MCT increased RV systolic pressure and hypertrophy, and lung arteriole wall thickness, fibrosis and leukocyte infiltration in the MCT group compared to the CTL group. All treatments improved these effects significantly. Furthermore, MCT reduced antioxidant factors, Bax, P21 and miR-204 expression and increased Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6) and Bcl-2. All of these effects were recovered by combination treatments. Conclusion: The results showed that combination therapy with subeffective/ ineffective doses of these compounds had ameliorative effects against PAH. [ABSTRACT FROM AUTHOR]

In this paper, we examine intraspecific variation in the quantity of alkaloid chemical defence in field collected individuals of the polymorphic ladybird beetle Adalia decempunctata (10-spot ladybird). Like its more widely studied relative Adalia bipunctata (2-spot ladybird), A. decempunctata possesses the alkaloids adaline and adalinine, which are, respectively, the major and minor alkaloids of A. bipunctata. We focused especially on alkaloid concentration in relation to colour pattern morph, sex, and the relationship between female and egg parameters. There was a marked sexual dimorphism in the balance of the two alkaloids, with adaline predominating in females and adalinine predominating in males: in males, on average, over 70% of total alkaloid was adalinine. Females had a lower proportion of adalinine (< 10%) than their eggs (> 15%) and relationships between egg alkaloid and female alkaloid or fecundity were weak or non-existent. Colour pattern morph had a borderline (although not) significant relationship with adaline concentration and total alkaloid concentration, which could be further explored with laboratory reared individuals. The sexual dimorphism in alkaloid content, which seems likely due to differences in synthesis, might be related to their relative costs to the two sexes and might provide insight into the evolution of alkaloid diversity in ladybirds. [ABSTRACT FROM AUTHOR]

Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are distinct herbs outlined by the Chinese Pharmacopoeia. They are sourced from the same plant but harvested at different times, resulting in differences in efficacy. It is important to avoid mixing them clinically and to distinguish between the two. Furthermore, dissimilar cultivation conditions may cause variability in the quality of herbs, so it is vital to differentiate drugs from dissimilar origins. In this study, two plants, AF and AFI from different provinces, were comparatively analyzed based on High Performance Liquid Chromatography (HPLC) fingerprints and classified using chemometric methods. The results indicate that the two medicines can be clearly distinguished. Also, AF and AFI grown in different locations can be distinguished. Ten chemical markers were screened, and their variations were determined, including eriocitrin, narirutin, naringin, meranzin hydrate, naringenin, hesperidin, nobiletin, tangeretin, neohesperidin, and poncirin. Subsequent network pharmacology correlated the screened chemical components with the biological network of the organism. The material basis of the difference in efficacy of the two homologous herbs was explored from the perspective of changes in chemical composition. This study provides a reference for formulating quality evaluation standards for AF and AFI and lays a foundation for the efficacy-related quality research of the two. [ABSTRACT FROM AUTHOR]

We established an efficient method using high-speed countercurrent chromatography (HSCCC) combined with preparative high-performance liquid chromatography (prep-HPLC) for isolating and purifying Gelsemium elegans (G. elegans) alkaloids. First, the two-phase solvent system composed of 1% triethylamine aqueous solution/n-hexane/ethyl acetate/ethanol (volume ratio 4:2:3:2) was employed to separate the crude extract (350 mg) using HSCCC. Subsequently, the mixture that resulted from HSCCC was further separated by Prep-HPLC, resulting in seven pure compounds including: 14-hydroxygelsenicine (1, 12.1 mg), sempervirine (2, 20.8 mg), 19-(R)-hydroxydihydrogelelsevirine (3, 10.1 mg), koumine (4, 50.5 mg), gelsemine (5, 32.2 mg), gelselvirine (6, 50.5 mg), and 11-hydroxyhumanmantenine (7, 12.5 mg). The purity of these seven compounds were 97.4, 98.9, 98.5, 99, 99.5, 96.8, and 85.5%, as determined by HPLC. The chemical structures of the seven compounds were analyzed and confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H-nuclear magnetic resonance (1H NMR), and 13 C-nuclear magnetic resonance (13 C NMR) spectra. The results indicate that the HSCCC-prep-HPLC method can effectively separate the major alkaloids from the purified G. elegans, holding promising prospects for potential applications in the separation and identification of other traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

Twelve compounds, comprising of four new ones, 6β,7α-limondiol (1) and ethyl 19-hydroxyisoobacunoate diosphenol (2), N-benzoyl 3-prenyltyramine (9) and 9-O-methyl integrifoliodiol (12), were isolated from the twigs with leaves of Tetradium trichotomum. The structures were elucidated by analysis of MS, NMR, and single-crystal X-ray diffraction. Compounds 1, 6, 8, 9 and 12 exhibited immunosuppressive activities in vitro against the proliferation of ConA-induced T lymphocytes and LPS-induced B cells. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6) was a potential target for Alzheimer's disease (AD). In this study, a series of novel oxyevodiamine-based HDAC6 inhibitors with a variety of linker moieties were designed, synthesized and evaluated. Compound 12 with a benzyl linker was identified as a high potent and selective HDAC6 inhibitor. It inhibited HDAC6 with an IC50 value of 6.2 nM and was more than 200 fold selectivity over HDAC1. It also had lower cytotoxicity and higher anti-H2O2 activity in vitro comparing with other derivatives. Compound 12 might be a good lead as novel HDAC6 inhibitor for the treatment of AD. [ABSTRACT FROM AUTHOR]

The present work aimed to evaluate three varieties of peanut (Arachis hypogaea L.) regarding the content of anthocyanins and total phenolics, antioxidant activity, phenolic profile and the alkaloids trigonelline and theobromine. The total phenolic content was analyzed by the Fast-Blue and Folin–Ciocalteau methods, while the antioxidant activity was analyzed by the β-carotene/linoleic acid, ABTS+ and FRAP methods. The phenolic profile and alkaloids were determined using high performance liquid chromatography (HPLC–DAD-UV–Vis). Peanuts with beige shells stood out with higher antioxidant activity and total phenolic content, while peanuts with purple shells stood out with higher anthocyanin content. Eight phenolic compounds and the alkaloids trigonelline and theobromine have been identified in peanut varieties. However, only four phenolics (gallic, syringic, ferulic and transcinnamic acids), in addition to the two alkaloids, were identified simultaneously in the three varieties studied. Chlorogenic acid was absent in red and purple-seeded varieties, catechin and resveratrol in varieties with red and beige coats, and p-coumaric acid in those with beige coats. For the first time, trigonelline and theobromine were identified in peanuts. Therefore, the bioactive composition and antioxidant activity of peanuts depend on its genotype. [ABSTRACT FROM AUTHOR]

Mitragyna speciosa is a perennial plant native to Asia, well known for its psychoactive properties. Its major alkaloid mitragynine is known to have sedative and euphoric effects. Hence, the plant has been a subject of abuse, leading to addiction, necessitating efficient analytical methods to detect its psychoactive constituents. However, current chromatography‐based methods for detecting the alkaloids are time consuming and costly. Quantitative nuclear magnetic resonance (qNMR) spectroscopy emerges as a promising alternative due to its nondestructive nature, structural insights, and short analysis time. Hence, a rapid and precise qNMR method was developed to quantify selected major psychoactive alkaloids in various parts of M. speciosa. Mitragynine, specioliatine, and speciogynine were quantified in relation to the integral value of the ‐OCH3 groups of the alkaloids and the internal standard 1,4‐dinitrobenzene. The precision and reproducibility of the method gave a relative standard deviation (RSD) of 2%, demonstrating the reliability of the method. In addition, the method showed excellent specificity, sensitivity, high linearity range (R2 = 0.999), and limits of detection (LOD) and quantification (LOQ) values. The analysis revealed that the red‐veined M. speciosa leaves contained higher levels of mitragynine (32.34 mg/g), specioliatine (16.84 mg/g) and speciogynine (7.69 mg/g) compared to the green‐veined leaves, stem bark, or fruits. [ABSTRACT FROM AUTHOR]

Fungi play a fundamental role in the marine environment, being promising producers of bioactive molecules in the pharmacological and industrial fields, which have demonstrated potential health benefits against cardiovascular and other chronic diseases. This review pertains to the analysis of the lipid compositions across various species of marine fungi and their constantly discovered substances, as well as their anti-inflammatory, antioxidant, and antithrombotic effects. The health-promoting aspects of these microorganisms will be explored, through the investigation of several mechanisms of action and interference of their bioactives in biochemical pathways. Despite exceptional results in this field, the potential of marine microorganisms remains largely unexplored due to the limited number of specialists in marine microbiology and mycology, a relatively recent science with significant contributions and potential in biodiversity and biotechnology. [ABSTRACT FROM AUTHOR]

As a widely occurring natural product, alkaloids have garnered increasing attention in drug research and development. The efficient, convenient, and environmentally friendly separation and detection of alkaloid compounds from diverse natural products has garnered increasing attention in recent research. Molecular imprinting technology (MIT) is recognized as an effective method for the selective extraction and separation of alkaloids from complex samples due to its capacity for specific recognition. To date, no comprehensive review has been published on the separation and purification of alkaloids using MIT, particularly regarding the sustainability aspects of this technology. In this paper, we review the general preparation methods of molecularly imprinted polymers (MIPs) for alkaloids, including bulk polymerization, precipitation polymerization, magnetic polymerization, and emulsion polymerization. Additionally, we summarize various applications of MIPs for alkaloids, such as different forms of MIP‐based solid phase extraction (MISPE) and MIP‐based sensors for alkaloids detection. Finally, we address some unresolved issues and anticipate future developments in the field. [ABSTRACT FROM AUTHOR]

Three sulfur-containing alkaloids aplospojaveedins A-C (1-3) with a hitherto undescribed carbon skeleton comprising octahy-dronaphthalene, α, β-unsaturated lactam and glycine-cysteine moieties were isolated from Aplosporella javeedii. Their structures were elucidated by 1D and 2D NMR spectroscopy, HR-MS, X-ray diffraction analysis, DFT-NMR and TDDFT-ECD calculations. A plausible biosynthetic pathway and putative targets are described. The blind docking suggested that 1-3 may have functional effects on several putative targets such as the GPCR cannabinoid receptor 2 or the integrin α5β1 complex. [ABSTRACT FROM AUTHOR]

Cancer is a major global health challenge, being the second leading cause of morbidity and mortality after cardiovascular disease. The growing economic burden and profound psychosocial impact on patients and their families make it urgent to find innovative and effective anticancer solutions. For this reason, interest in using natural compounds to develop new cancer treatments has grown. In this respect, antofine, an alkaloid class found in Apocynaceae, Lauraceae, and Moraceae family plants, exhibits promising biological properties, including anti-inflammatory, anticancer, antiviral, and antifungal activities. Several molecular mechanisms have been identified underlying antofine anti-cancerous effects, including the inhibition of nuclear factor κB (NF-κB) and AKT/mTOR signaling pathways, epigenetic inhibition of protein synthesis, ribosomal targeting, induction of apoptosis, inhibition of DNA synthesis, and cell cycle arrest. This study discusses the molecular structure, sources, photochemistry, and anticancer properties of antofine in relation to its structure–activity relationship and molecular targets. Then, examine in vitro and in vivo studies and analyze the mechanisms of action underpinning antofine efficacy against cancer cells. This review also discusses multidrug resistance in human cancer and the potential of antofine in this context. Safety and toxicity concerns are also addressed as well as current challenges in antofine research, including the need for clinical trials and bioavailability optimization. This review aims to provide comprehensive information for more effective natural compound-based cancer treatments. [ABSTRACT FROM AUTHOR]

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction. [ABSTRACT FROM AUTHOR]

Daphenylline, a structurally unique triterpenoid Daphniphyllum alkaloid, has attracted considerable attention from the synthetic community since its isolation. Herein, we delineate an enantioselective total synthesis of (−)‐daphenylline, which is based on a gold‐catalyzed dearomatization reaction of β‐methoxynaphthalene. Other features include installation of the initial chiral stereocenter via an enantioselective rhodium‐catalyzed hydrogenation of an alkylidene‐indane derivative; construction of the other vital stereocenter by organocatalytic asymmetric Mukaiyama–Michael reaction of a structurally complex benzofused cyclohexanone; and a tandem reductive amination/amidation double cyclization reaction to assemble the distinctive azapolycyclic cage‐like architecture. [ABSTRACT FROM AUTHOR]

The selective borylation of specific C−H bonds in organic synthesis remains a formidable challenge. In this study, we present a novel spirobipyridine ligand that features a binaphthyl backbone. This ligand facilitates the iridium‐catalyzed selective C−H borylation of benzene derivatives. The ligand is designed with "side‐arm‐wall" substituents that allow vicinal di‐ or multi‐substituted benzene derivatives to approach metal center and effectively block other reactive sites by non‐covalent interactions with substrates. The effectiveness of this strategy is demonstrated by the successful selective distal C−H activation of various alkaloids and its broad compatibility with functional groups. [ABSTRACT FROM AUTHOR]

This study develops a biogenetic synthesis strategy using electrooxidation and heterodimerization of N-substituted pyrrolidine-1-carboxamides to create diverse analogues of the fissoldhimine alkaloid core. Under acidic conditions, 2-alkoxypyrrolidine-1-carboxamides from Shono oxidation formed endo-heterodimers with high yields and diastereoselectivity. Enantioselective heterodimerization using chiral phosphoric acid catalysis produced exo-heterodimers with high enantioselectivity. [ABSTRACT FROM AUTHOR]

A diversity-oriented total synthesis for Amaryllidaceae alkaloids incorporating the frequently found C3a-arylated hydroindole moiety was developed. Chiral-anion-induced gold(I) catalysis was employed for the cyclization of 1,4-diynes to the pyrrolidine and the installation of the all-carbon quaternary stereocenter. Both enantiomeric series of crinine-type alkaloids in high enantiopurity were accessible by this methodology. The formal synthesis of a wide range of Amaryllidaceae alkaloids is described, such as (+)-vitattine, (–)- epi -vitattine, (–)-elwesein, (–)- epi -elwesein, (–)-crinine, (–)- epi -crinine, (–)-buphanisine, (–)-flexinine, and (+)-gracilamine. [ABSTRACT FROM AUTHOR]

Reported herein is the first total synthesis of the poly‐pseudoindoxyl natural product baphicacanthcusine A. The synthesis leverages the oxidative rearrangement of indoles to pseudoindoxyls to install vicinal pseudoindoxyl heterocycles in a diastereoselective manner. Key steps include an acid‐mediated cyclization/indole transposition, two diastereoselective oxidative ring contractions, and a site‐selective C−H oxygenation. The synthesis of the oxidation precursors was guided by recognition of an element of hidden symmetry. This work provides a foundation for the chemical synthesis of other poly‐pseudoindoxyl alkaloids. [ABSTRACT FROM AUTHOR]

An unprecedented dyotropic rearrangement of β‐lactams has been developed, which provides an enabling tool for the synthesis of structurally diverse γ‐butyrolactams. Unlike the well‐established dyotropic rearrangements of β‐lactones, the present reaction probably proceeds through a dual‐activation mode, and thus displays unusual reactivity and chemoselectivity. The combined computational and experimental results suggest that the dyotropic rearrangement of β‐lactams may proceed through different mechanisms depending on the nature of migrating groups (H, alkyl, or aryl). Hinging on a chemoselective H‐migration dyotropic rearrangement of β‐lactams, we have completed the divergent synthesis of tricyclic marine alkaloids (−)‐lepadiformine A, (+)‐cylindricine C, and (−)‐fasicularin within 11–12 longest linear steps. [ABSTRACT FROM AUTHOR]

Background: Issues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study. Methods: Thirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results. Results: The alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R2 = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter_gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples (P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050). Conclusions: These findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients. Chinese clinical trial registry: No. ChiCTR2300067507. Registered on January 10,2023 retrospectively. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-β/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of highquality studies, significant progress will be made in the treatment of fibrosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the phytochemical content and toxicity profile of Rauwolfia vomitoria Afze (Apocynaceae). Method: Qualitative phytochemical screening of hydro-alcohol extract (HAE) of R. vomitoria roots was carried out followed by acute toxicity evaluation in nine Swiss albino Wistar rats using two phases of Lorke's method. In the 14 days subacute study, thirty-two Swiss albino rats were randomly divided into 4 groups of 8 rats each. Group A received 0.5 mL Tween 80 daily and served as control, while groups B, C and D was administered 125, 250 and 500 mg/kg/day of HAE respectively. All the rats were monitored daily for signs of toxicity. Selected haematological and biochemical parameters were assessed at the termination of experiment. Results: Alkaloids, cardiac glycosides, flavonoids and saponins were present in HAE. The estimated oral median lethal dose (LD50) was greater than 5000 mg/kg. Daily administration of HAE for 14 days resulted in 15.63 % mortality of animals across the groups by day 14 with significant loss in total body weight in group D animals on day 8 (p < 0.05), and in group C animals on day 11 (p < 0.05) and day 15 (p < 0.001). The dose of 500 mg/kg/day significantly (p < 0.05) increased haemoglobin concentration but reduced (p < 0.05) white blood cell count, while the dose of 250 mg/kg/day significantly (p < 0.05) reduced alkaline phosphatase levels but increased serum albumin levels (p < 0.05). Conclusion: Rauwolfia vomitoria may be safe on acute basis but repeated administration of high doses over many days needs to be done with caution. [ABSTRACT FROM AUTHOR]

Microorganisms remain in water from various sources after desalination and other treatments, posing health risks. We explored alternative natural disinfection agents, focusing on grape seed extract (GSE). We collected local grape seeds in Saudi Arabia and analyzed their chemical components. Using gas chromatography–mass spectrometry and inductively coupled plasma mass spectrometry, we identified essential phytochemicals in the GSE, including polyphenols, flavonoids, and alkaloids. Notably, the GSE was free from bacteria and heavy-metal contamination and rich in beneficial nutrient metals. We conducted qualitative analyses on local water and urine samples to detect bacterial infections, heavy metals, and minerals. To assess GSE's antibacterial potential, we performed molecular docking analysis. Our results reveal a strong binding energy between GSE and bacterial protein receptors, parallel to that of standard antibiotics. Additionally, the results of the laboratory pilot investigations align with those of computational analyses, confirming GSE's efficacy. Agar well diffusion tests demonstrated significantly greater zones of inhibition for the crude oil extract compared with both diluted GSE and the positive control against the bacteria detected in the water and urine samples. Furthermore, we identified contamination by four bacterial strains and heavy metals in water samples and female urine samples, highlighting the need for effective water disinfectants. GSE shows promise as a safe and potent natural water disinfectant. [ABSTRACT FROM AUTHOR]

Background/Objectives: Annona squamosa is used in folk medicine to treat pain and arthritis. Palmatine is an alkaloid isolated from several plants, including A. squamosa leaves. The aim of the present study was to investigate the analgesic, anti-arthritic, and anti-inflammatory potential of the methanolic extract of A. squamosa (EMAS) and palmatine. Methods: The chemical profile of EMAS was evaluated by ultra high-performance liquid chromatography with electrospray ionization coupled to mass spectrometry (UHPLC-ESI/MS). EMAS and palmatine were evaluated in carrageenan-induced pleurisy, zymosan-induced joint inflammation, formalin-induced nociception, and tumor necrosis factor (TNF)-induced mechanical hyperalgesia in experimental models in mice. A cytotoxicity test of EMAS and palmatine was performed using a methylthiazolidiphenyl-tetrazolium (MTT) bromide assay. Results: The analysis of the chemical profile of the extract showed the presence of palmatine, liriodenine, and anonaine. Oral administration of EMAS and palmatine significantly reduced leukocyte migration and oxide nitric production in the carrageenan-induced pleurisy model. EMAS and palmatine reduced mechanical hyperalgesia, leukocyte migration, and edema formation in the joint inflammation induced by zymosan. In the formalin test, palmatine was effective against the second-phase nociceptive response, mechanical hyperalgesia, and cold allodynia. In addition, palmatine reduced mechanical hyperalgesia induced by TNF. EMAS and palmatine did not demonstrate cytotoxicity. Conclusions: The present study showed that A. squamosa and palmatine are analgesic and anti-inflammatory agents, and that the anti-hyperalgesic properties of palmatine may involve the TNF pathway. Palmatine may be one of the compounds responsible for the anti-hyperalgesic and/or anti-arthritic properties of this medicinal plant. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is one of the complications of diabetes. This study was conducted to investigate the effect of curcumin-piperine on laboratory factors and macular vascular in DR. Materials and Methods: The present study was a randomized, placebo-controlled, double-blind, parallel-arm clinical trial that was conducted on 60 patients with DR aged 30-65 years. Patients were randomized into two groups to receive (i) 1010 mg/day of curcumin-piperine (two tablets per day, each tablet containing 500 mg curcuminoids and 5 mg piperine) (n = 30) or (ii) the matched placebo (n = 30) for 12 weeks. The investigated factors included optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), oxidative stress factors, C-reactive protein (CRP), fasting blood glucose (FBG), triglycerides (TGs), blood urea nitrogen (BUN), and creatinine. Results: The trial was completed by 27 patients in the intervention group and 29 patients in the placebo group. Curcumin-piperine significantly increased total antioxidant capacity (0.86 ± 0.66 vs. 0.45 ± 0.89; P = 0.022) and superoxide dismutases (0.77 ± 2.11 vs. -0.45 ± 3.08; P = 0.031), while it decreased and malondialdehyde (MDA) (-1.06 ± 5.80 vs. 1.89 ± 6.12; P = 0.043) and creatinine (-0.04 ± 0.16 vs. 0.03 ± 0.05; P = 0.042) compared with placebo. However, this supplement had no significant effect on CRP, FBG, TG, BUN, OCT, and OCTA. There were no adverse reactions. Conclusion: Curcumin-piperine is effective in improving oxidative stress and reducing creatinine in DR. Further trials are necessary to confirm these promising findings. [ABSTRACT FROM AUTHOR]