Insight into the sorption and desorption pattern of pyrrolizidine alkaloids and their N-oxides in acidic tea (Camellia sinensis) plantation soils.

Pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) are phytotoxins produced by various plant species and have been emerged as environmental pollutants. The sorption/desorption behaviors of PAs/PANOs in soil are crucial due to the horizontal transfer of these natural products from PA-producing plants to soil and subsequently absorbed by plant roots. This study firstly investigated the sorption/desorption behaviors of PAs/PANOs in tea plantation soils with distinct characteristics. Sorption amounts for seneciphylline (Sp) and seneciphylline-N-oxide (SpNO) in three acidic soils ranged from 2.9 to 5.9 µg/g and 1.7 to 2.8 µg/g, respectively. Desorption percentages for Sp and SpNO were from 22.2% to 30.5% and 36.1% to 43.9%. In the mixed PAs/PANOs systems, stronger sorption of PAs over PANOs was occurred in tested soils. Additionally, the Freundlich models more precisely described the sorption/desorption isotherms. Cation exchange capacity, sand content and total nitrogen were identified as major influencing factors by linear regression models. Overall, the soils exhibiting higher sorption capacities for compounds with greater hydrophobicity. PANOs were more likely to migrate within soils and be absorbed by tea plants. It contributes to the understanding of environmental fate of PAs/PANOs in tea plantations and provides basic data and clues for the development of PAs/PANOs reduction technology.

Dissecting molecular mechanisms underlying the inhibition of ß-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives.

ß-Glucuronidase, a crucial enzyme in drug metabolism and detoxification, represents a promising target for therapeutic intervention due to its potential to modulate drug pharmacokinetics and enhance therapeutic efficacy. Herein, we assessed the inhibitory potential of phytochemicals from Hibiscus trionum against ß-glucuronidase. Grossamide and grossamide K emerged as the most potent ß-glucuronidase inhibitors with IC50 values of 0.73 ± 0.03 and 1.24 ± 0.03 µM, respectively. The investigated alkaloids effectively inhibited ß-glucuronidase-catalyzed PNPG hydrolysis through a noncompetitive inhibition mode, whereas steppogenin displayed a mixed inhibition mechanism. Molecular docking analyses highlighted grossamide and grossamide K as inhibitors with the lowest binding free energy, all compounds successfully docked into the same main binding site occupied by the reference drug Epigallocatechin gallate (EGCG). We explored the interaction dynamics of isolated compounds with ß-glucuronidase through a 200 ns molecular dynamics (MD) simulation. Analysis of various MD parameters revealed that grossamide and grossamide K maintained stable trajectories and demonstrated significant energy stabilization upon binding to ß-glucuronidase. Additionally, these compounds exhibited the lowest average interaction energies with the target enzyme. The MM/PBSA calculations further supported these findings, showing the lowest binding free energies for grossamide and grossamide K. These computational results are consistent with experimental data, suggesting that grossamide and grossamide K could be potent inhibitors of ß-glucuronidase.

Identifying plant-derived antiviral alkaloids as dual inhibitors of SARS-CoV-2 main protease and spike glycoprotein through computational screening.

COVID-19 is currently considered the ninth-deadliest pandemic, spreading through direct or indirect contact with infected individuals. It has imposed a consistent strain on both the financial and healthcare resources of many countries. To address this challenge, there is a pressing need for the development of new potential therapeutic agents for the treatment of this disease. To identify potential antiviral agents as novel dual inhibitors of SARS-CoV-2, we retrieved 404 alkaloids from 12 selected medicinal antiviral plants and virtually screened them against the renowned catalytic sites and favorable interacting residues of two essential proteins of SARS-CoV-2, namely, the main protease and spike glycoprotein. Based on docking scores, 12 metabolites with dual inhibitory potential were subjected to drug-likeness, bioactivity scores, and drug-like ability analyses. These analyses included the ligand-receptor stability and interactions at the potential active sites of target proteins, which were analyzed and confirmed through molecular dynamic simulations of the three lead metabolites. We also conducted a detailed binding free energy analysis of pivotal SARS-CoV-2 protein inhibitors using molecular mechanics techniques to reveal their interaction dynamics and stability. Overall, our results demonstrated that 12 alkaloids, namely, adouetine Y, evodiamide C, ergosine, hayatinine, (+)-homoaromoline, isatithioetherin C, N,alpha-L-rhamnopyranosyl vincosamide, pelosine, reserpine, toddalidimerine, toddayanis, and zanthocadinanine, are shortlisted as metabolites based on their interactions with target proteins. All 12 lead metabolites exhibited a higher unbound fraction and therefore greater distribution compared with the standards. Particularly, adouetine Y demonstrated high docking scores but exhibited a nonspontaneous binding profile. In contrast, ergosine and evodiamide C showed favorable binding interactions and superior stability in molecular dynamics simulations. Ergosine demonstrated exceptional performance in several key pharmaceutical metrics. Pharmacokinetic evaluations revealed that ergosine exhibited pronounced bioactivity, good absorption, and optimal bioavailability. Additionally, it was predicted not to cause skin sensitivity and was found to be non-hepatotoxic. Importantly, ergosine and evodiamide C emerged as superior drug candidates for dual inhibition of SARS-CoV-2 due to their strong binding affinity and drug-like ability, comparable to known inhibitors like N3 and molnupiravir. This study is limited by its in silico nature and demands the need for future in vitro and in vivo studies to confirm these findings.

Therapeutic Potential of Solanum Alkaloids with Special Emphasis on Cancer: A Comprehensive Review.

Cancer has emerged as a formidable global health challenge, with treatment methods like chemotherapy and radiation often exacerbating the situation due to their associated side effects. Opting for natural sources like plants as a safer and environmentally friendly alternative seems promising. Historically, plants have served as valuable sources for treating diverse health conditions, attributable to their rich composition of therapeutic phytochemicals. Within this array of phytochemicals, alkaloids, especially those found in the Solanaceae plant family, are notably prominent. Alkaloids from Solanaceae plant family called Solanum alkaloids demonstrate noteworthy anti-tumour characteristics and exert a potent inhibitory influence on cancer cell proliferation. They trigger programmed cell death in cancerous cells through various molecular pathways, whether administered alone or combined with other medications. Solanum alkaloids act upon cancer cells via multiple mechanisms, including apoptosis induction, suppression of cell growth and migration, as well as inhibition of angiogenesis. This review provides insights into the anti-cancer attributes of Solanum alkaloids found in various Solanum plant species, along with a brief overview of their other medicinal properties.

Detection of vinblastine and related bioactive compounds from culture extracts of endophytic fungi of Catharanthus roseus.

This study investigates the synthesis of vinblastine by endophytic fungi isolated from leaf of C. roseus. A total of 10 endophytic fungi were selected for secretion of vinca alkaloids based on the initial screening by biochemical tests and thin-layer chromatography (TLC). Out of these ten, only four fungal extracts showed positive results for presence of vinblastine at same retention time (10 min.) compared to reference compound on HPLC analysis. The detected concentration of vinblastine was maximum (17 µg/ml) in isolate no. CRL 22 followed by CRL 52, CRL 17 and CRL 28. To validate the presence of vinblastine, ultra-high-performance liquid chromatography coupled with high-resolution accurate mass spectrometry (HRMS) was employed. This analysis confirmed the presence of anhydrovinblastine, a precursor of vinblastine through the detection of molecular ions at m/z 793.4185 in extract of CRL 17. In addition to anhydrovinblastine, the intermediate compounds essential to the biosynthetic pathway of vinblastine were also detected in the extract of CRL 17. These host-origin compounds strongly suggest the presence of a biosynthetic pathway within the endophytic fungus. Based on morphological observation and sequence analysis of the ITS region of rDNA, endophytic fungi were identified as Alternaria alternata (CRL 17), Curvularia lunata (CRL 28), Aspergillus terrus (CRL 52), and Aspergillus clavatonanicus (CRL 22).

Developing benzylisoquinoline alkaloid-enriched opium poppy via CRISPR-directed genome editing: A review.

Among plant-derived secondary metabolites are benzylisoquinoline alkaloids (BIAs) that play a vital role in medicine. The most conspicuous BIAs frequently found in opium poppy are morphine, codeine, thebaine, papaverine, sanguinarine, and noscapine. BIAs have provided abundant clinically useful drugs used in the treatment of various diseases and ailments With an increasing demand for these herbal remedies, genetic improvement of poppy plants appears to be essential to live up to the expectations of the pharmaceutical industry. With the advent of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9), the field of metabolic engineering has undergone a paradigm shift in its approach due to its appealing attributes, such as the transgene-free editing capability, precision, selectivity, robustness, and versatility. The potentiality of the CRISPR system for manipulating metabolic pathways in opium poppy was demonstrated, but further investigations regarding the use of CRISPR in BIA pathway engineering should be undertaken to develop opium poppy into a bioreactor synthesizing BIAs at the industrial-scale levels. In this regard, the recruitment of RNA-guided genome editing for knocking out miRNAs, flower responsible genes, genes involved in competitive pathways, and base editing are described. The approaches presented here have never been suggested or applied in opium poppy so far.

A Major Facilitator Superfamily Transporter Contributes to Ergot Alkaloid Accumulation but Not Secretion in Aspergillus leporis.

Ergot alkaloids are fungal natural products with important roles in agriculture and medicine. We used heterologous expression and gene knockout approaches to investigate potential roles for the product of a major facilitator superfamily transporter gene (easT) recently found in an ergot alkaloid biosynthetic gene cluster in Aspergillus leporis. A strain of Aspergillus fumigatus previously engineered to accumulate lysergic acid, but which did not convert the precursor agroclavine to lysergic acid efficiently or secrete lysergic acid well, was chosen as an expression host for easT. Expression of easT in this strain resulted in accumulation of significantly more pathway intermediates but no detectable lysergic acid. Secretion of ergot alkaloids was reduced in the easT-expressing strain. EasT localized to discrete vesicle-like structures in the cytosol of A. fumigatus, with no localization detected in the plasma membrane. When easT was knocked out in A. leporis, accumulation of lysergic acid amides was reduced relative to the wild type. There was no negative effect on secretion of ergot alkaloids in the knockout mutant. The data indicate that easT encodes a product that contributes to accumulation of ergot alkaloids, perhaps by transporting intermediates between cellular compartments, but does not have a significant role in secreting ergot alkaloids.

In-vitro hepatotoxic activity of mitragynine and paynantheine isolated from the leaves of Mitragyna speciosa Korth. (Kratom).

Mitragynine, a primary alkaloid found in kratom leaves has been reported to have a broad range of pharmacological and toxicological properties while its congener, paynatheine has comparatively less information available on these aspects. Mitragynine and its congener, paynantheine, were isolated from the ethanol kratom leaves extract using gravity column chromatography techniques. Our study evaluated the cytotoxicity potential of mitragynine and paynantheine on normal human liver cell line, HL-7702, and human hepatoma cell line, HepG2. Mitragynine exhibited a moderate inhibitory effect on the HepG2 cell line with IC50 value of 42.11 ± 1.31 µM in comparison with vinblastine (IC50: 15.45 ± 0.72 µM) while it showed non-cytotoxic properties towards the HL-7702 cell line with concentrations ranging below 200 µM. In contrast, paynantheine exhibited weak cytotoxic properties towards HepG2 and HL-7702 cell lines. Further comprehensive evaluations of both compounds are needed to establish more details on the cytotoxicity potential of kratom alkaloids.

New insights into the chemistry and anticancer activity of Ophiocordyceps xuefengensis.

Ophiocordyceps xuefengensis (O. xuefengensis), the sister taxon of Ophiocordyceps sinensis (O. sinensis), is consumed as a "tonic food" due to its health benefits. However, little is known regarding the chemistry and bioactivity of O. xuefengensis. In this study, we characterized 80 indole-based alkaloids in the ethyl acetate fraction of O. xuefengensis by high performance liquid chromatography-quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS/MS), of which 54 indole-based alkaloids were identified as possibly new compounds. Furthermore, 29 of these compounds were established as potential anti-cancer compounds by ligand fishing combined with HPLC-Q-TOF-MS/MS. Moreover, molecular docking identified the NH- and OH- groups of these compounds as the key active groups. The present study has expanded the knowledge on the characteristic indole-based alkaloids and anti-cancer activity of O. xuefengensis.

Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

Alkaloid profiling of the new species Corydalis huangshanensis and other 13 medicinal plants in genus Corydalis.

INTRODUCTION: Corydalis DC., the largest genus of Papaveraceae, comprises numerous species known for their abundant alkaloid content and historical use in clinical medicine. Recently, a new species of genus Corydalis named Corydalis huangshanensis Lu Q. Huang & H. S. Peng was discovered in the Huangshan Mountains of Anhui Province, China. OBJECTIVE: To compare the chemical characteristics of C. huangshanensis and other 13 Corydalis species, aiming to elucidate the potential medicinal value of this new species. MATERIALS AND METHODS: The chemical constituents of C. huangshanensis and other 13 medicinal plants of genus Corydalis were analyzed using ultra-high-performance liquid chromatography Q-Exactive Plus hybrid quadrupole-Orbitrap mass spectrometer (Q-Orbitrap) mass technology. The differences in the alkaloids in the 14 species were distinguished by chemometrics. RESULTS: The mass spectrometry fragmentation information and relative content of 72 alkaloids were obtained. Orthogonal partial least squares discriminant analysis (OPLS-DA) and cluster heat mapping analysis showed that these 14 species were divided into two groups. The clustering relationship between C. huangshanensis and C. decumbens (Thunb.) Pers. was similar, exhibiting similar chemical compositions and characteristics. These results indicate the potential pharmacological effects of C. huangshanensis. CONCLUSION: This study enhances our understanding of the chemical classification of Corydalis and provides a basis for speculations on the medicinal value of C. huangshanensis.

Natural Bioactive Compounds in the Management of Periodontal Diseases: A Comprehensive Review.

Periodontal diseases, chronic inflammatory conditions affecting oral health, are primarily driven by microbial plaque biofilm and the body's inflammatory response, leading to tissue damage and potential tooth loss. These diseases have significant physical, psychological, social, and economic impacts, necessitating effective management strategies that include early diagnosis, comprehensive treatment, and innovative therapeutic approaches. Recent advancements in biomanufacturing have facilitated the development of natural bioactive compounds, such as polyphenols, terpenoids, alkaloids, saponins, and peptides, which exhibit antimicrobial, anti-inflammatory, and tissue regenerative properties. This review explores the biomanufacturing processes-microbial fermentation, plant cell cultures, and enzymatic synthesis-and their roles in producing these bioactive compounds for managing periodontal diseases. The integration of these natural compounds into periodontal therapy offers promising alternatives to traditional treatments, potentially overcoming issues like antibiotic resistance and the disruption of the natural microbiota, thereby improving patient outcomes.

[Effect of different initial processing treatments on commercial characters and chemical components of Fritillaria taipaiensis].

To investigate the effects of different initial processing methods on the quality of Fritillaria taipaiensis, this study explored the effects of anti-browning treatment, drying methods, and drying temperatures on the commercial characters, chromaticity values, and alkaloid and nucleoside components of Fritillariae Taipaiensis Bulbus. The results were comprehensively evaluated through correlation analysis(CA), principal component analysis(PCA), and hierarchical clustering analysis(HCA). Compared with those of the direct drying group(WD60), the chromaticity values(ΔE*) of the groups with scraped outer skin( FHB1) and mixed lime powder treatments(FHB2) were significantly reduced, indicating the inhibition of the browning process. The total alkaloid content of the group with mixed raw soil treatment(FHB3) and the FHB2 group showed no significant change, whereas that of the group with 5%Na Cl O solution rinse treatment(FHB4) was the lowest. Compared with air-blast dried(WD50) samples, the ΔE* values of freezedried(FS6) and vacuum-dried(FS5) samples were significantly decreased, with an increase in total alkaloid contents. Conversely,the ΔE* values of shade-dried(FS1) and sun-dried(FS2) samples were significantly increased, with severe browning and low total alkaloid contents. The total alkaloid contents of heat-pump-dried(FS4) samples showed no significant change, and their ΔE* value was significantly decreased, with a light degree of browning and favorable commercial characters. The total alkaloid content of air-blast dried samples initially increased and then decreased within the range of 40-80 ℃, and the highest content was recorded at 70 ℃. The ΔE* values of high-temperature air-blast dried samples(70-80 ℃) were smaller with a light degree of browning, whereas their texture was compact and lacked powder. CA revealed a significant relationship between the uracil content and chromaticity value of the samples(P< 0. 05). The clustering relationships among samples subjected to different treatments were visualized via PCA and HCA. The results showed that FHB2 and air-blast drying(50-60 ℃) were more suitable for large-scale production, and heat pump drying could be a promising direction for future development. This study provides a scientific basis for optimizing the initial processing methods of Fritillaria taipaiensis.

Microencapsulation of roasted mate tea extractives with lasiodiplodan (a (1 → 6)-ß-D-glucan) and maltodextrin as combined coating materials: A strategic tool to stabilize and protect the bioactive components.

Microencapsulation has emerged as a promising strategy to enhance the stability and protection of bioactive compounds. In this work, roasted mate tea was microencapsulated using 15 % maltodextrin and lasiodiplodan (0.5-1.25 %) as wall coating materials. The microcapsules were characterized for encapsulation efficiency, hygroscopicity, moisture, water activity, water solubility, dissolubility, scanning electron microscopy, FT-IR spectroscopy, thermal analysis, colorimetry, antioxidant activity, as well as quantification of phenolic compounds and caffeine. Microencapsulation yields ranged from 44.92 to 56.39 %, and encapsulation efficiency varied from 66.54 to 70.16 by increasing the lasiodiplodan concentration. FT-IR revealed phenolic acids, flavonoids, and polyphenolics. Minor color variations were observed among the samples. Thermal analysis demonstrated the microencapsulates exhibited good thermal stability with no degradation below 250 °C. Encapsulated samples showed high levels of bioactive compounds, suggesting that microencapsulation by spray-drying was a favorable process, where maltodextrin, a low-cost protective agent, when combined with the properties of lasiodiplodan, can be a good option for stabilizing mate extracts.

Genomic and Cell-Specific Regulation of Benzylisoquinoline Alkaloid Biosynthesis in Opium Poppy.

Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine and papaverine. Most enzymes involved in benzylisoquinoline alkaloids (BIAs) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition.

The Bitter Truth: How Insects Cope with Toxic Plant Alkaloids.

Plants are unique organisms that have developed ingenious strategies to cope with environmental challenges, such as herbivorous insects. One of these strategies is the synthesis of a vast array of chemical compounds, known as specialized metabolites, that serve many ecological functions. Among the most fascinating and diverse groups of specialized metabolites are the alkaloids, which are characterized by the presence of a nitrogen atom within a heterocyclic ring. While some have medicinal and recreational applications, others are highly unpalatable and/or toxic. The effects of alkaloids on both humans and insects can be very diverse, affecting their physiology and behavior. Insects that feed on alkaloid-containing plants have evolved diverse mechanisms to cope with the consequences of these toxins. These include sequestration, where insects store alkaloids in specialized tissues or organs, enzymatic detoxification through enzymes such as cytochrome P450 monooxygenases and glutathione S-transferases, and behavioral adaptations such as selective feeding. In this review, we explore the relationships between plant alkaloids and the evolutionary adaptations that enable insects to exploit alkaloid-rich plants as food sources and ecological niches minimizing the harmful effects of these natural compounds. We aim to provide a comprehensive and updated overview of this fascinating and complex ecological interaction.

Cephalostatins and ritterazines: Distinctive dimeric marine-derived steroidal pyrazine alkaloids with intriguing anticancer activities.

Cephalostatins and ritterazines represent fascinating classes of dimeric marine derived steroidal alkaloids with unique chemical structures and promising biological activities. Originally isolated from marine tube worms and the tunicate Ritterella tokioka collected off the coast of Japan, cephalostatins and ritterazines display potent anticancer effects by inducing apoptosis, disrupting cell cycle progression, and targeting multiple molecular pathways. This review covers the chemistry and bioactivities of 45 cephalostatins and ritterazines from 1988 to 2024, highlighting their complex structures and medicinal contributions. With insights into their structure activity relationships (SAR). Key structural elements, such as the pyrazine ring and 5/6 spiroketal moieties, are found crucial for their biological effects, suggesting interactions with lipid membranes or hydrophobic protein domains. Additionally, the formation of oxocarbenium ions from spiroketal cleavage may enhance their potency by covalently modifying DNA. The pharmacokinetics, ADMET and Drug likeness properties of these steroidal alkaloids are thoroughly addressed. Drug likeness analysis shows that these compounds fit well with the Rule of 4 (Ro4) for Protein-Protein Interaction Drugs (PPIDs), underscoring their potential in this area. Ten compounds (20, 27, 33, 34, 39, 40, 41, 42, 43, and 45) have demonstrated favourable pharmacokinetic and ADMET profiles, making them promising candidates for further research. Future efforts should focus on alternative administration routes, structural modifications, and innovative delivery systems, such as prodrugs and nanoparticles, to improve bioavailability and therapeutic effects. Advances in synthetic chemistry, mechanistic insights, and interdisciplinary collaborations will be essential for translating cephalostatins and ritterazines into effective anticancer therapies.

Combined analysis of the metabolome and transcriptome reveals the metabolic characteristics and candidate genes involved in alkaloid metabolism in Heuchera micrantha Douglas ex Lindl.

BACKGROUND: Alkaloids, important secondary metabolites produced by plants, play a crucial role in responding to environmental stress. Heuchera micrantha, a well-known plant used in landscaping, has the ability to purify air, and absorb toxic and radioactive substances, showing strong environmental adaptability. However, there is still limited understanding of the accumulation characteristics and metabolic mechanism of alkaloids in H. micrantha. RESULTS: In this study, four distinct varieties of H. micrantha were used to investigate the accumulation and metabolic traits of alkaloids in its leaves. We conducted a combined analysis of the plant's metabolome and transcriptome. Our analysis identified 44 alkaloids metabolites in the leaves of the four H. micrantha varieties, with 26 showing different levels of accumulation among the groups. The HT and JQ varieties exhibited higher accumulation of differential alkaloid metabolites compared to YH and HY. We annotated the differential alkaloid metabolites to 22 metabolic pathways, including several alkaloid metabolism. Transcriptome data revealed 5064 differentially expressed genes involved in these metabolic pathways. Multivariate analysis showed that four key metabolites (N-hydroxytryptamine, L-tyramine, tryptamine, and 2-phenylethylamine) and three candidate genes (Cluster-15488.116815, Cluster-15488.146268, and Cluster-15488.173297) that merit further investigation. CONCLUSIONS: This study provided preliminarily insight into the molecular mechanism of the biosynthesis of alkaloids in H. micrantha. However, further analysis is required to elucidate the specific regulatory mechanisms of the candidate gene involved in the synthesis of key alkaloid metabolites. In summary, our findings provide important information about how alkaloid metabolites build up and the metabolic pathways involved in H. micrantha varieties. This gives us a good starting point for future research on the regulation mechanism, and development, and utilization of alkaloids in H. micrantha.

Qualitative, Quantitative, In Vitro Antioxidant Activity and Chemical Profiling of Leptadenia pyrotechnica (Forssk.) Decne Using Advanced Analytical Techniques.

Leptadenia pyrotechnica Forssk. Decne (LP) is a medicinal herb from the Asclepiadaceae family with many advantageous properties. The goal of this research is to identify, quantify, and evaluate the antioxidant potential of LP to validate its remarkable therapeutic advantages. The hot soxhlet extraction method was employed to prepare different extracts of LP (stem and root). These extracts were evaluated physiochemically to check their impurity, purity, and quality; qualitatively to detect different phytochemicals; and quantitatively for phenol, saponin, tannin, flavonoid, and alkaloid contents. Then, the in vitro antioxidant potential was estimated by DPPH, NO, H2O2 scavenging assays, and MC and FRAP assays. The most prevalent phytochemicals of LP were then analysed by AAS, FT-IR, UV-visible, and GC-MS techniques. A higher extractive yield was shown by LPSE and LPRE (7.37 ± 0.11 and 5.70 ± 0.02). The LP stem showed better physicochemical and qualitative results than the root. The quantitative and in vitro antioxidant results indicated maximal phenols, tannins, and alkaloid contents in LPSE, which was further confirmed by UV-visible, FT-IR, and GC-MS results. The extraction methods (soxhlation or ultrasonication) were optimized by utilizing RSM to determine the impacts of multiple parameters. The study concluded that the plant has remarkable therapeutic advantages to promote additional clinical investigations and the mechanisms of its action.

Ramulus Mori (Sangzhi) Alkaloids Alleviate Diabetic Nephropathy through Improving Gut Microbiota Disorder.

Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.