Alkaloid Piperine Research Articles

Volatile and non-volatile metabolite profiling of under-explored crop Piper colubrinum link. With chromatography mass spectrometry approach and its biochemical diversity from medicinally valued Piper species

Piper colubrinum Link. is an underexplored crop regarding its metabolites and therapeutic attributes. Current study aimed to identify the possible volatile and non-volatile metabolites of P. colubrinum fruit and studied its metabolite diversity with medicinally valued Piper species viz. P. nigrum L., P. longum L. and P. chaba Hunter. The volatile constituents of P. colubrinum essential oil by GC–MS revealed the presence of sesquiterpenes as the major contribution. The sesquiterpenes α-muurolol (12.5 %) and β-caryophyllene (11.3 %) were the predominant volatile components. Few aliphatic compounds like n-heptadecane and trace amounts of monoterpenes (α- and β-pinene and α-terpineol) were also identified from this crop. The fatty acid profiling by GC–MS revealed mainly oleic acid (41.3 %) followed by palmitic and linoleic acids. HPLC analysis demonstrated that the major pungent alkaloid piperine was found to be trace (0.04 %) in P. colubrinum. The LC-QTOF-MS/MS profiling of the chloroform extract of the P. colubrinum revealed the presence of non-volatile constituents including phenolic and alkaloid compounds. Ferulic acid, rosmarinic acid, salicylic acid, kaempferol-5-glucoside, 5-methoxysalicylic acid, apigenin-7-galactoside, kaempferide-3-glucoside, luteolin, kaempferol, apigenin and scutellarein-4′-methyl ether were the phenolic compounds whereas piperlonguminine was the alkaloid compound identified. Finally, the biochemical parameters of this crop were compared with that of P. nigrum, P. longum and P. chaba and average linkage cluster dendrogram revealed that P. colubrinum was biochemically distinct from other three Piper species.

Piperine, quercetin, and curcumin identified as promising natural products for topical treatment of cutaneous leishmaniasis

Leishmania braziliensis (L. braziliensis) causes cutaneous leishmaniasis (CL) in the New World. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administer. Topical treatment would be the ideal option for the treatment of CL. This underscores the urgent need for affordable and effective treatments, with natural compounds being explored as potential solutions. The alkaloid piperine (PIP), the polyphenol curcumin (CUR), and the flavonoid quercetin (QUE), known for their diverse biological properties, are promising candidates to address these parasitic diseases. Initially, the in vitro cytotoxicity activity of the compounds was evaluated using U-937 cells, followed by the assessment of the leishmanicidal activity of these compounds against amastigotes of L. braziliensis. Subsequently, a golden hamster model with stationary-phase L. braziliensis promastigote infections was employed. Once the ulcer appeared, hamsters were treated with QUE, PIP, or CUR formulations and compared to the control group treated with meglumine antimoniate administered intralesionally. We observed that the three organic compounds showed high in vitro leishmanicidal activity with effective concentrations of less than 50 mM, with PIP having the highest activity at a concentration of 8 mM. None of the compounds showed cytotoxic activity for U937 macrophages with values between 500 and 700 mM. In vivo, topical treatment with QUE daily for 15 days produced cured in 100% of hamsters while the effectiveness of CUR and PIP was 83% and 67%, respectively. No failures were observed with QUE. Collectively, our data suggest that topical formulations mainly for QUE but also for CUR and PIP could be a promising topical treatment for CL. Not only the ease of obtaining or synthesizing the organic compounds evaluated in this work but also their commercial availability eliminates one of the most important barriers or bottlenecks in drug development, thus facilitating the roadmap for the development of a topical drug for the management of CL caused by L. braziliensis.

Tissue-specific variations of piperine in ten populations of Piper longum L.: bioactivities and toxicological profile

P. longum L., one of the most significant species of the genus Piperaceae, is most frequently employed in Indian-Ayurvedic and other traditional medicinal-systems for treating a variety of illnesses. The alkaloid piperine, is the key phytoconstituent of the plant, primarily responsible for its’ pharmacological-impacts. The aim of the study is to analyse the intra-specific variation in piperine content among different chemotypes (PL1 to PL 30) and identify high piperine yielding chemotype (elite-chemotype) collected from 10 different geographical regions of West Bengal by validated HPTLC chromatography method. The study also focused on the pharmacological-screening to better understand the antioxidant activity of the methanol extracts of P. longum by DPPH and ABTS radical-scavenging activity and genotoxic activity by Allium cepa root tip assay. It was found that the P. longum fruit chemotypes contain high amount piperine (highest 16.362 mg/g in chemotype PL9) than the stem and leaf chemotypes. Both DPPH and ABTS antioxidant assays revealed that P. longum showed moderate radical-scavenging activity and the highest activity was found in PL9 (fruit) chemotype with IC50 values of 124.2 ±0.97\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm 0.97$$\\end{document} and 104 ±0.78\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm 0.78$$\\end{document} µg/ml respectively. The A. cepa root tip assay showed no such significant genotoxic-effect and change in mitotic-index. The quick, reproducible, and validated HPTLC approach offers a useful tool for determining quantitative variations of piperine among P. longum chemotypes from different geographical-regions and also according to the different tissues and choose elite genotypes with high piperine production for continued propagation and commercialization for the pharmaceutical sector. Additionally, the plant's in-vitro antioxidant property and lack of genotoxicity directly supports its’ widespread and long history of use as a medicinal and culinary plant.

Review on the Pharmacological Activities of Black Pepper

Black pepper (Piper nigrum (L.), Family: Piperaceae) which is considered as the king of spices is well known for its pungent odour and has gained a global consideration. Traditional uses of pepper include the treatment of piles, worms, diarrhoea, intermittent fever, cough, cold, dyspnea, and throat conditions. The bioactive components of pepper like pungent alkaloid piperine as well as its essential oil possess numerous pharmacological properties, including hypolipidemic, antibacterial, neuroprotective, anticancer, anticonvulsant, analgesic, with anti-inflammatory effects and so on. This review focuses on the research that has been carried out on black pepper’s chemical content, recent advancements in chemistry and its pharmacological effects.

Effective pickering emulsifiers based on submicron carboxymethyl cellulose/chitosan polymer particles

In this study, cross-linked carboxymethyl cellulose/chitosan submicron particles were employed to facilitate the stabilization of Pickering emulsion. The polymer particles were prepared using the polyelectrolyte self-assembly method in conjunction with isocyanide based multicomponent reactions and the characteristics were obtained using: nuclear magnetic resonance, Fourier-transform infrared spectroscopy and dynamic light scattering. Atomic force microscopy revealed the heterogeneous structure of the resulting submicron particles with domains of 20–30 nm in size. The average diameter was found to be in the range of 229–378 nm and they were found to be suitable for the fabrication of oil/water Pickering emulsion when proceeded via the homogenization method followed by sonication. The results obtained revealed that carboxymethyl cellulose/chitosan particles significantly stabilized the droplets at the oil/water interface. Even at low particle concentrations of 0.3 g/L (which is close to that of low molecular weight surfactants) stable Pickering emulsions have been obtained. Additionally, the resulting emulsions showed a high level of stability with regard to changes in pH, temperature and ionic strength. The natural alkaloid piperine was used as a model compound to load the resulting particles, which possessed encapsulation efficiency of 90.6±0.4%. Furthermore, the in vitro release profile of piperine from the Pickering emulsion revealed a much-controlled release in both acidic and neutral media as compared to the unformulated piperine. Additional findings in this work revealed important information on the application of carboxymethyl cellulose/chitosan submicron particles as Pickering stabilizers for creation of new delivery systems.

A simple and reliable QSPR model for prediction of chromatography retention indices of volatile organic compounds in peppers.

Worldwide, various types of pepper are used in food as an additive due to their unique pungency, aroma, taste, and color. This spice is valued for its pungency contributed by the alkaloid piperine and aroma attributed to volatile essential oils. The essential oils are composed of volatile organic compounds (VOCs) in different concentrations and ratios. In chromatography, the identification of compounds is done by comparing obtained peaks with a reference standard. However, there are cases where reference standards are either unavailable or the chemical information of VOCs is not documented in reference libraries. To overcome these limitations, theoretical methodologies are applied to estimate the retention indices (RIs) of new VOCs. The aim of the present work is to develop a reliable QSPR model for the RIs of 273 identified VOCs of different types of pepper. Experimental retention indices were measured using comprehensive two-dimensional gas chromatography coupled to quadrupole mass spectrometry (GC × GC/qMS) using a coupled BPX5 and BP20 column system. The inbuilt Monte Carlo algorithm of CORAL software is used to generate QSPR models using the hybrid optimal descriptor extracted from a combination of SMILES and HFG (hydrogen-filled graph). The whole dataset of 273 VOCs is used to make ten splits, each of which is further divided into four sets: active training, passive training, calibration, and validation. The balance of correlation method with four target functions i.e. TF0 (WIIC = WCII = 0), TF1 (WIIC = 0.5 & WCII = 0), TF2 (WIIC = 0 & WCII = 0.3) and TF3 (WIIC = 0.5 & WCII = 0.3) is used. The results of the statistical parameters of each target function are compared with each other. The simultaneous application of the index of ideality of correlation (IIC) and correlation intensity index (CII) improves the predictive potential of the model. The best model is judged on the basis of the numerical value of R2 of the validation set. The statistical result of the best model for the validation set of split 6 computed with TF3 (WIIC = 0.5 & WCII = 0.3) is R2 = 0.9308, CCC = 0.9588, IIC = 0.7704, CII = 0.9549, Q2 = 0.9281 and RMSE = 0.544. The promoters of increase/decrease for RI are also extracted using the best model (split 6). Moreover, the proposed model was used for an external validation set.

In vitro anti-parasitic effect of the alkaloids harmaline and piperine on Toxoplasma gondii.

Toxoplasma gondii is a coccidian protozoan of zoonotic importance that causes toxoplasmosis. Although the current treatments for toxoplasmosis may be associated with adverse effects and limited efficacy for different biological forms of the parasite, evidence suggests that alkaloid molecules such as harmaline and piperine exhibit antiparasitic effects against protozoa parasites. This investigation aimed to evaluate the in vitro effect of harmaline and piperine against T. gondii tachyzoites in infected Vero cell cultures. After 24 hours of host cell infection, the cultures were treated with harmaline or piperine (0.49 to 15.63 µg/mL). Negative and positive controls were RPMI/DMSO (0.1%) and sulfadiazine (200 µg/mL). Harmaline significantly reduced parasite multiplication by 20% compared to the negative control, while piperine decreased between 55.56% and 88.89% in a dose-dependent manner. According to an intracellular parasite proportion scale, it was observed that the Vero cells with low or moderate parasitic proliferation were more prevalent after the alkaloid treatment. The study demonstrated that the alkaloids had antiparasitic effects on T. gondii, with piperine being the most effective. Additional studies must be carried out to clarify other aspects of the action of the alkaloids on parasites.

Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

In vitro and in vivo efficacy of Larrea divaricata extract for the management of Phytophthora palmivora in olive trees

Phytophthora palmivora is a ubiquitous pathogen responsible for “dry branch” disease, causing significant economic losses in olive trees. Synthetic chemical fungicides are currently used for the control of P. palmivora. The general concern about the negative consequences of using synthetic products prioritizes the search for eco-friendly alternatives. In this context, plant extracts have emerged as an interesting and promising alternative for crop protection. This work studies the inhibitory activity of Larrea divaricata extract on P. palmivora mycelial growth, sporangium and zoospore production. The extract showed fungicidal activity against P. palmivora mycelial growth at concentrations over 150 mg mL-1. Specifically, the extract at 50 mg mL-1 completely suppressed the production of P. palmivora sporangia and zoospores. The alkaloid piperine in L. divaricata extract showed antimicrobial activity against P. palmivora mycelial growth. Extract effectiveness was also evaluated on olive trees in a greenhouse, showing 63% of disease reduction. These results support the use of L. divaricata extract as another environmentally friendly tool to be included in an integrated disease management program for dry branch disease caused by P. palmivora. Highlights: L. divaricata extract showed an effective antimicrobial activity against P. palmivora. Piperine was identified in the divaricata extract by HPLC/MWD. The alkaloid piperine in divaricata extract showed antimicrobial activity on the mycelial growth of P. palmivora. L. divaricata extract could be included in an integrated management programme for dry branch disease caused by P. palmivora.

Comparative transcriptome profiling of fruit tissue provides novel insights into piperine biosynthesis in black pepper (Piper nigrum L.)

Black pepper (Piper nigrum L.) is a storehouse of numerous bioactive compounds, most important being the alkaloid piperine. This metabolite has immense applications in both food and pharmaceutical industries. Therefore, studying the pathways involved in piperine biosynthesis is of paramount importance for improving the piperine content in black pepper. In the present study, we have estimated the piperine content across different fruit/berry developmental stages (DS1 to DS8) and leaf tissue of two different traditional landraces of black pepper, using the high-performance liquid chromatography (HPLC) method. Based on the results obtained, the landrace Thottumuriyan was identified to possess higher piperine content amongst the two landraces with high piperine content detected at the mid-developmental stages. The fruit tissues spanning the different developmental stages (DS2, DS4, DS6 and DS8) were selected for comparative transcriptome profiling. An average of 150 million read pairs were generated for the five different samples (4 berry development stages and the leaf tissue). These were mapped against the black pepper reference genome and differentially expressed genes (DEGs) were identified for the four different combinations. Further transcript profiling of twenty candidate genes potentially involved in secondary metabolite biosynthesis pathways, including piperine synthesis, was performed using Real time PCR in the eight different berry developmental stages. Highest expression for the genes associated with piperine biosynthesis was observed at mid-developmental stages. This included the genes coding for piperine synthase and piperic acid-CoA ligase. Our data provides critical information to understand the molecular mechanisms underlying piperine biosynthesis and other pathways in black pepper.

Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer's Disease.

The naturally inspired multitarget-directed ligands (PC01-PC10 and PD01-PD26) were synthesized from piperine for the management of Alzheimer's disease (AD). The compound PD07 showed significant inhibitory activity on ChEs, BACE1, and Aβ1-42 aggregation in in vitro studies. Further, compound PD07 effectively displaced the propidium iodide at the AChE PAS site. The compound PD07 exhibited significant lipophilicity in PAMPA studies. Additionally, PD07 demonstrated neuroprotective properties in the Aβ1-42 induced SH-SY5Y cell line. Furthermore, DFT calculations were performed using B3LYP/6-311G(d,p) basis sets to explore the PD07 physical and chemical properties. The compound PD07 showed a similar binding interaction profile at active sites of AChE, BuChE, and BACE1 proteins as compared to reference ligands (donepezil, tacrine, and BSD) in molecular docking and dynamic simulation studies. In acute oral toxicity studies, compound PD07 exhibited no toxicity symptoms up to 300 mg/kg, po. The compound PD07 (10 mg/kg, po) improved memory and cognition in scopolamine-induced amnesia rats. Further, PD07 increased ACh levels in the brain by inhibiting the AChE activity. The results from in vitro, in silico, and in vivo studies suggested that compound PD07 is a potent multitarget-directed lead from piperine to overcome Alzheimer's disease.

High Value-Added Application of Natural Plant Products in Crop Protection: Construction and Pesticidal Activities of Piperine-Type Ester Derivatives and Their Toxicology Study

To discover new potential pesticide candidates, recently, structural modification of natural bioactive products has received much attention. In this work, a series of new piperine-type ester derivatives were regio- and stereoselectively synthesized based on a natural alkaloid piperine isolated from Piper nigrum. Their structures were characterized by IR, mp, 1H NMR (13C NMR), and high-resolution mass spectrometry (HRMS). Against Tetranychus cinnabarinus Boisduval (Acari: Tetranychidae), compounds 4e, 4f, 4u, and 4v displayed the most significant acaricidal activity with LC50 values of 0.155, 0.117, 0.177, and 0.164 mg/mL, respectively. Particularly, compound 4f showed >120-fold higher acaricidal activity than piperine (LC50: 14.198 mg/mL). Notably, the acaricidal activity of 4f was equivalent to that of the commercial acaricide spirodiclofen (LC50: 0.115 mg/mL). Additionally, against Eriosoma lanigerum Hausmann (Hemiptera: Aphididae), compounds 4w and 4b' showed 1.8-fold aphicidal activity of piperine. Furthermore, via the scanning electron microscope (SEM) imaging method, the obvious destruction of the construction of the cuticle layer of 4f-treated T. cinnabarinus was observed. Compound 4f could be further studied as a lead acaricidal agent.

Therapeutic Potential of Bioactive Compounds of Piper nigrum L. (Black Pepper): A Review

The present study highlights the Bio activities and Pharmacology of Piper nigrum L. (Black Pepper). Piper nigrum L is commonly known as Kali Mirch, Pippali, Milagu Peppercorn, White pepper, Green pepper, Black pepper, and Madagascar pepper longum plant is a deciduous slender aromatic climber. The major source of bioactive constituents in black pepper is present in the fruits. It contains major pungent alkaloid piperine (1-peperoyl piperidine) which is known to possess pharmacological actions. Antimicrobial activity of black pepper evaluated the antibacterial potential of aqueous decoction of Piper nigrum L. (black pepper), against different bacterial isolates from oral cavity of individual volunteers.

Thermodynamic and electrochemical investigation of inhibition efficiency of green corrosion inhibitor and its comparison with synthetic dyes on MS in acidic medium

The expedition of Green corrosion inhibitors has been initiated by the organic corrosion inhibitor as green corrosion inhibitors are bio-degradable, eco-friendly and environmental acceptable bereft of heavy metals and other toxic products. Moreover, the products obtained from the plant are cost-effective, readily available and can be renewed. In the following study, the inhibition performance of natural inhibitor i.e., black pepper extract and synthetic inhibitors i.e., thoron Dye and Phenosafranin dye on mild steel surfaces in hydrochloric acid (HCl) were inspected and for this purpose, weight loss measurements, Electrochemical Impedance Measurements (EIS) and Potentiodynamic Polarization study at different concentrations and at different temperatures were recruited. Among these inhibitors, the best inhibition efficiency was shown by black pepper extract i.e., 97% in 1 M HCl. In the prolongation of our work, entropy (ΔS), enthalpy (ΔH), gibbs free energy (ΔG), activation energy (Ea) and pre-exponential factor (A) of the reaction were calculated and it is concluded that the inhibition process follows physical adsorption on the surface and the adsorption process follows Langmuir and Tempkin isotherms also. For surface analysis, Atomic Force Microscopy (AFM) was done. The present study concludes that natural inhibitor i.e., Black pepper extract which contains alkaloid piperine becomes quite impressive in decelerating the effect of corrosion on mild steel surfaces in acidic environments as compared to synthetic inhibitors.

Pepper Alkaloid Piperine Increases Radiation Sensitivity of Cancer Cells from Glioblastoma and Hypopharynx In Vitro.

In our study, our aim was to examine the cytotoxic and radio-sensitizing effect of the alkaloid piperine, a major pungent of black pepper, on two different human epithelial tumor cell lines in vitro. The growth of the human cell lines T98G (glioblastoma) and FaDu (hypopharyngeal carcinoma) was examined under the influence of piperine in different concentrations. In addition, after combined treatment with ionizing radiation, long-term survival was investigated with a colony formation assay. The proliferation was analyzed using the BrdU-assay, while the DNA repair capacity was examined via the γH2AX assay. Piperine reduced the growth of both cell lines in a concentration-dependent manner as well as a time-dependent one. After combined treatment with piperine and ionizing radiation, an inhibition of clonogenic survival could be proven. A reduced proliferation capacity and an additive effect on DNA damage 24 h after irradiation are possible causal mechanisms, which were also demonstrated for both cell lines. Based on the results presented in this study, piperine was shown to have cytotoxic antitumor activity and a radio-sensitizing effect in micromolar concentrations in the human tumor cells that were tested. Based on these results piperine represents a potential therapeutic option in radio-oncological treatment.

Synthesis and antihyperlipidaemic activity of a new piperine derivative

Long pepper (Piper longum Linn.) is widely used as a medicinal substance in traditional Ayurvedic medicine. Its major alkaloid piperine is the main active constituent with various therapeutic activities and has low solubility in water. In this study, a soluble new derivative of a piperine alkaloid, named N-leucinylpiperamide was synthesized. The animal experiment showed that N-leucinylpiperamide has more hypolipidemic effects than commercially available simvastatin and piperine in modulating serum lipids in Wistar male rats. At the amount of 10 mg/kg bw, it significantly reduced TC (-52.4%), TG (-61.7%), and LDL-C (-27.8%), respectively, and increased HDL-C (+147.4%) in the serum of the high-lipid model group. Furthermore, the synthesized N-leucinylpiperamide had no noticeable cytotoxicity against HepG2 cell line in vitro. Thus, our study shows that N-leucinylpiperamide has an ability to improve serum lipid profile in hyperlipidemic model rats and could be a valuable promising agent for the preventing hyperlipidemia.

EXTRACTION, ISOLATION, CHEMICAL IDENTIFICATION AND IN VITRO UROLITHIATIC ACTIVITY OF PIPERINE FROM PIPER NIGRUM

Piper nigrum is belongs to the family Piperaceae. The aim of the present study was to extract, isolate and investigate in vitro urolithiatic activity of alkaloid (piperine) from black pepper and identification by chemical reagents. In vitro urolithiatic evaluation of piperine was performed by percentage dissolution and turbidity methods. Calcium oxalate crystals were synthetically prepared and packed in a semipermeable membrane in both methods. Results were compared statistically and it showed significant P​

Neuroprotective Effects of Black Pepper Cold-Pressed Oil on Scopolamine-Induced Oxidative Stress and Memory Impairment in Rats.

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement.

Antiarthritic Activities of Herbal Isolates: A Comprehensive Review

Numerous plant isolates with therapeutic properties, such as antimicrobial, antiinflammatory, antiviral, antimalarial, antiarthritic (AA), hepatoprotective, cardiotonic, and so forth, are reported in the literature. Usually, medicinal plants are widely used, and assumed to be safe and cheaper alternatives to chemically synthesized drugs. However, they are not regulated for potency and purity, and thus care must be taken for their safe use. In this review, we aimed to compile all of the herbal isolates possessing AA properties, including alkaloids (montanine, 3-acetylaconitine, sanguinarine, jatrorrhizine hydrochloride, and piperine), terpenoids (eugenol, nimbolide, bartogenic acid, cannabidiol, and curcumin), and flavonoids (quercetin, resveratrol, kaempferol, chebulanin, ellagic acid, rosmarinic acid, gallic acid, chlorogenic acid, ferulic acid, and brazilin). These isolates act through numerous pharmacological mechanisms such as inhibiting cytokines, chemokines, or matrix metalloproteinase, etc., to demonstrate AA activity. Animal models utilized for assessing the AA properties of these isolates, including adjuvant-induced arthritis mouse models, are also discussed. Furthermore, nanotechnology-based approaches to deliver these isolates are also reviewed, which have shown improved therapeutic efficacy of isolated compounds.

In vitro anthelmintic evaluation of three alkaloids against gastrointestinal nematodes of goats

This study assessed the in vitro anthelmintic activity of the alkaloids berberine, harmaline and piperine on gastrointestinal nematodes (GIN) of goat and their possible cytotoxic effects in Vero cells. The anthelmintic evaluation was performed using the egg hatch (EHA) and larval motility (LMA) assays. Cytotoxicity was determined using the 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-tetrazolium bromide (MTT) assay. The alkaloids berberine and piperine inhibited the hatching of GIN eggs in more than 90 %. Piperine was the most active compound against goat GIN eggs with an EC50 (effective concentration 50 %) of 0.0074 mM (0.0021 mg/mL), while the EC50 of berberine was 1.32 mM (0.49 mg/mL). Harmaline (EC50 = 1.6 mM – 0.34 mg/mL) showed moderate ovicidal action (80.30 %). In LMA, piperine and harmaline reduced larval motility in 2.75 and 25.29 %, respectively. Larvicidal efficacy was evidenced only with the alkaloid berberine, which showed a percentage of inhibition of larval motility of 98.17 % (2.69 mM =1.0 mg/mL). In the MTT assay, all alkaloids showed low toxicity to Vero cells, with a percentage of cell viability greater than 50 % in all concentrations tested. These results suggest that berberine and piperine have anthelmintic potential on goat gastrointestinal nematodes with low toxicity to mammalian cells.