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Monoterpenoid indole alkaloids (MIAs) represent a major class of active ingredients from the plants of the genus Gelsemium. Gelsemium MIAs with diverse chemical structures can be divided into six categories: gelsedine-, gelsemine-, humantenine-, koumine-, sarpagine- and yohimbane-type. Additionally, gelsemium MIAs exert a wide range of bioactivities, including anti-tumour, immunosuppression, anti-anxiety, analgesia, and so on. Owing to their fascinating structures and potent pharmaceutical properties, these gelsemium MIAs arouse significant organic chemists' interest to design state-of-the-art synthetic strategies for their total synthesis. In this review, we comprehensively summarised recently reported novel gelsemium MIAs, potential pharmacological activities of some active molecules, and total synthetic strategies covering the period from 2013 to 2022. It is expected that this study may open the window to timely illuminate and guide further study and development of gelsemium MIAs and their derivatives in clinical practice.

Rationale Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom ( Mitragyna Speciosa ), there is a lack of clinical trials in humans. Objectives This phase 1 study aimed to evaluate mitragynine’s safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance. Methods A placebo-controlled, single-blind, within-subjects study was conducted in two parts. In part A, eight healthy human volunteers received placebo and three doses of mitragynine (5, 10, and 20 mg) in a sequential dosing scheme, on separate days. In part B, a second group of seven volunteers received placebo and 40 mg of mitragynine. Vital signs, subjective drug experience, neurocognitive function, and pain tolerance were measured at regular intervals for 7 h after administration. Results Overall, mitragynine did not affect most of the outcome measures at any dose. Yet, the lowest dose (5 mg) of mitragynine increased subjective ratings of arousal and attention, accuracy in a sustained attention task, and motor inhibition. The highest dose (40 mg) of mitragynine increased subjective ratings of amnesia and produced mild psychopathological symptoms. Mitragynine did not significantly affect vital signs, and only mild, transient side effects were reported. Conclusion The present study suggests that low doses (5–10 mg) of mitragynine may cause subjective feelings of stimulation and enhance attention, while the highest dose (40 mg) may cause inhibitory feelings of amnesia and distress. Mitragynine doses up to 40 mg were well tolerated in this group.

Aconitum pendulum Busch (Tiebangchui), a traditional Chinese medicinal herb, is recognized for its diverse pharmacological properties and for its significant toxicity. The Zanba stir-frying processing method is commonly employed to mitigate toxicity and enhance efficacy; however, the underlying chemical principles remain insufficiently studied. In order to address this issue, a phytochemical investigation was conducted on the diterpenoid alkaloids present in Zanba-processed Tiebangchui. Eleven diterpenoid alkaloids were isolated by means of chromatographic techniques, including silica gel column chromatography. Their structures were elucidated by extensive spectroscopic analysis (single-crystal X-ray diffraction, IR, HR-ESI-MS) and comparison with literature data. The compounds were identified as 12-epi-turpelline (1), 12-epi-napelline (2), 12-acetyl-napelline (3), azitine (4), flavaconitine (5), nagarutine C (6), nagarutine D (7), 16-epi-pyroaconine (8), spicatine B (9), 3-deoxyaconitine (10), and napelline (11). Notably, compound 1 was characterized as a novel alkaloid. Additionally, compounds 3–9 were isolated from this processed material for the first time. These findings provide crucial chemical insights into the detoxification mechanism of Zanba processing. Subsequent pharmacological evaluation revealed that compounds 10 and 11 exhibit notable anti-inflammatory activities. Moreover, given the structural analogy between the novel alkaloid 1 and the active compound 11, compound 1 is proposed as a promising lead for future structure–activity relationship studies and semi-synthetic modification.

Mitragynine is an “atypic opioid” analgesic with an alternative mechanism of action and a favorable side-effect profile. Our aim was to optimize the alkaloid extraction procedure from kratom leaves and to determine and isolate the most relevant compounds capable of penetrating the central nervous system. The PAMPA-BBB study revealed that mitragynine and its coalkaloids, speciociliatine, speciogynine, and paynantheine, possess excellent in vitro BBB permeability. An optimized sequence of CPC, flash chromatography, and preparative HPLC methods was used to isolate the four identified BBB+ alkaloids. To improve the bioavailability of the isolated alkaloids, their cyclodextrin (CD) complexation behavior was investigated via affinity capillary electrophoresis using almost 40 CD derivatives. The apparent alkaloid–CD complex stability constants were determined and compared, and the most relevant CDs phase-solubility studies were also performed. Both the neutral and negatively charged derivatives were able to form complexes with all four kratom alkaloids. It was found that cavity size, substituent type, and degree of substitution also influenced complex formation. The negatively charged Sugammadex, Subetadex, and the sufoalkylated-beta-CD analogs were able to form the most stable complexes, exceeding 1000 M−1. These results serve as a good basis for further solubility and stability enhancement studies of kratom alkaloids.

RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses.

Catharanthus roseus is a medicinal plant that produces indole alkaloids, which are utilized in anticancer therapy. Vinblastine and vincristine, two commercially important antineoplastic alkaloids, are mostly found in the leaves of Catharanthus roseus. ĸ-carrageenan has been proven as plant growth promoting substance for a number of medicinal and agricultural plants. Considering the importance of ĸ-carrageenan as a promoter of plant growth and phytochemical constituents, especially alkaloids production in Catharanthus roseus, an experiment was carried out to explore the effect of ĸ-carrageenan on the plant growth, phytochemicals content, pigments content, and production of antitumor alkaloids in Catharanthus roseus after planting. Foliar application of ĸ-carrageenan (at 0, 400, 600 and 800 ppm) significantly improved the performance of Catharanthus roseus. Phytochemical analysis involved determining the amount of total phenolics (TP), flavonoids (F), free amino acids (FAA), alkaloids (TAC) and pigments contents by spectrophotometer, minerals by ICP, amino acids, phenolic compounds and alkaloids (Vincamine, Catharanthine, Vincracine (Vincristine), and vinblastine) analysis uses HPLC. The results indicated that all examined ĸ-carrageenan treatments led to a significant (p ≤ 0.05) increase in growth parameters compared to the untreated plants. Phytochemical examination indicates that the spray of ĸ-carrageenan at 800 mg L−1 increased the yield of alkaloids (Vincamine, Catharanthine and Vincracine (Vincristine)) by 41.85 μg/g DW, total phenolic compounds by 3948.6 μg gallic/g FW, the content of flavonoids 951.3 μg quercetin /g FW and carotenoids content 32.97 mg/g FW as compared to the control. An amount of 400 ppm ĸ-carrageenan treatment gave the best contents of FAA, Chl a, Chl b and anthocyanin. The element content of K, Ca, Cu, Zn and Se increased by treatments. Amino acids constituents and phenolics compounds contents were altered by ĸ-carrageenan.

•Type 2 diabetes is associated with dyslipidemia and elevated cardiovascular risk.•Curcuminoids are bioactive polyphenolic natural products.•The impact of curcuminoids on serum lipids in diabetic subjects was investigated.•Curcuminoids supplementation reduced serum non-HDL-cholesterol and Lp(a).•Curcuminoids may reduce cardiovascular risk in diabetic subjects. Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n = 118) were assigned to curcuminoids (1000 mg/day plus piperine 10 mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (−21.86 ± 25.78 versus −17.06 ± 41.51, respectively; p = 0.023), non-HDL-C (−23.42 ± 25.13 versus −16.84 ± 41.42, respectively; p = 0.014) and Lp(a) (−1.50 ± 1.61 versus −0.34 ± 1.73, respectively; p = 0.001) and elevations in serum HDL-C levels (1.56 ± 4.25 versus −0.22 ± 4.62, respectively; p = 0.048) in the curcuminoids group as compared with the placebo group (p < 0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p > 0.05). Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a pivotal role in producing pro-inflammatory eicosanoids, including prostaglandins (PGs) and leukotrienes (LTs), in the inflammation process. Mitragynine is a primary alkaloid contained in the kratom’s leaves and has been reported to show anti-inflammatory activity by suppressing COX-2 mRNA translation to lowering PGs synthesis. In this study, the Kratom’s alkaloid extract containing ~ 46% mitragynine was found to exhibit dual inhibition activity towards COX-2/5-LOX enzymes at concentrations below 25 ppm in the LPS-induced RAW 264.7 macrophage cells. At these levels, no cell toxicity was observed while the cells became death (e.g., 10–46% viability at 50–100 ppm) and only COX-2 inhibition activity was observed after exposed with more than 25 ppm of alkaloid extract. In contrast, the methanolic-crude extract of Kratom’s leaf containing ~ 5% mitragynine showed no inhibition toward COX-2/5-LOX enzymes and did not toxic onto the cells, even after treated at 100 ppm. The alkaloid extract suppressed several antiinflammation parameters, including ROS (64% reduction at 25 ppm), NO (30% reduction at 25 ppm), TNF-α (~ 50% reduction at 25 ppm), and IL-6 production (60% reduction at 6.25 ppm). In silico molecular studies indicated strong binding affinity of Kratom alkaloids to COX-2 and 5-LOX active sites, supporting the Kratom’s alkaloids to have great potential dual inhibition activity towards COX-2/5-LOX enzymes and to be developed as a safer NSAIDs with fewer side effects.

Nineteen monoterpene indole alkaloids, including twelve new ones, were successfully isolated and identified from the stems and leaves of (Havil.). The planar structures were elucidated by nuclear magnetic resonance (NMR), high-resolution mass (HRMS), and ultraviolet (UV) analyses. The absolute configurations of new compounds were determined using electron circular dichroism calculations in conjunction with NMR calculations. The acetylcholinesterase inhibitory activity of the isolated compounds was evaluated in vitro. In further biological evaluation, the isolated compounds were evaluated for their neuroprotective effects on HT22 neuronal cells. Six compounds demonstrated significant protective activity. Their intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA fluorescent probe, which markedly attenuated glutamate-induced ROS accumulation. The results not only enrich the knowledge on the structural diversity of monoterpene indole alkaloids but also offer substantial evidence for further pharmacological exploration.

The magnetization strategy of isoquinoline alkaloids has been successfully used in the extraction and isolation, but the effect of the magnetization on biological activities of those alkaloids still deserves further investigation. Therefore, the antibacterial, lipid-lowering and antioxidant activities of five isoquinoline alkaloids (berberine, tetrahydroberberine, palmatine, tetrahydropalmatine and tetrahydropapavine) before and after magnetization were compared in this study, and the results showed that the relevant activities were enhanced after magnetization. Additionally, among the five magnetic derivatives studied, berberine magnetic derivative ([Ber·H] + [FeCl 4 ] − ) had the best antibacterial effect on S. aureus and E. coli with MIC of 200 and 800 µM, respectively; palmatine magnetic derivative ([Pal·H] + [FeCl 4 ] − ) showed the strongest lipid-lowering activity with IC50 of 429 mM, and the inhibitory effect and type on lipase was reversible and mixed inhibition of competition and non-competition type; tetrahydroberberine magnetic derivative ([THBer·H] + [FeCl 4 ] − ) had the strongest antioxidant activity. This study provides new ideas and references for the further application of magnetization strategy.