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Piperine is a plant-derived promising piperamide candidate isolated from the black pepper (Piper nigrum L.). In the last few years, this natural botanical product and its derivatives have aroused much attention for their comprehensive biological activities, including not only medical but also agricultural bioactivities. In order to achieve sustainable development and improve survival conditions, looking for environmentally friendly pesticides with low toxicity and residue is an extremely urgent challenge. Fortunately, plant-derived pesticides are rising like a shining star, guiding us in the direction of development in pesticidal research. In the present review, the recent progress in the biological activities, mechanisms of action, and structural modifications of piperine and its derivatives from 2020 to 2023 are summarized. The structure-activity relationships were analyzed in order to pave the way for future development and utilization of piperine and its derivatives as potent drugs and pesticides for improving the local economic development.

The objectives of this study were to prepare and characterize a novel piperine–succinic acid multicomponent crystal phase and to evaluate the improvement in the solubility and dissolution rate of piperine when prepared in the multicomponent crystal formation. The solid-state characterization of the novel multicomponent crystal was performed by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform-infrared (FT-IR) spectroscopy. Solubility and dissolution rate profiles were evaluated in distilled water. The physical stability was evaluated under high relative humidity (75% and 100% RH). The determination of the single crystal X-ray diffraction structure revealed that this novel multicomponent crystal was a cocrystalline phase of piperine–succinic acid (2:1 molar ratio). The differential scanning calorimetry thermogram of the cocrystal showed a single and sharp endothermic peak at 110.49 °C. The cocrystal resulted in greater solubility and a faster dissolution rate of piperine than intact piperine. This improvement was a result of the formation of a channel structure in the cocrystal. In addition, the cocrystal was stable under a humid condition.

Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.

Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, anti-thrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19. Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India. Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5 mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomes were assessed for the duration of hospitalization. Results: Patients with mild, moderate, and severe symptoms who received curcumin/piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group. Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events. Clinicaltrials.gov identifier: CTRI/2020/05/025482

Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, especially in advanced and metastatic stages where treatment options are limited. HJ-4, a novel piperine derivative, demonstrated strong tumor-selective inhibition. Within safe concentrations (cell viability > 85%), HJ-4 dose-dependently suppressed colony formation and DNA synthesis in CRC cells, showing potent anti-proliferative effects. It also significantly inhibited cell adhesion, wound healing, and invasion, indicating robust anti-migration and anti-invasion properties. In vivo, the CAM model confirmed that HJ-4 reduced both tumor volume and angiogenesis. Mechanistically, HJ-4 activated the p53-dependent apoptosis pathway while suppressing the Wnt/β-catenin axis and E2F transcriptional activity, effectively impeding tumor progression. Overall, HJ-4 exhibits promising tumor specificity and multiple antitumor mechanisms, supporting its potential for clinical development in CRC treatment.

Background Black pepper ( Piper nigrum L.), an important and long-cultivated spice crop, is native to South India and grown in the tropics. Piperine is the main pungent and bioactive alkaloid in the berries of black pepper, but the molecular mechanism for piperine biosynthesis has not been determined. MicroRNAs (miRNAs), which are classical endogenous noncoding small RNAs, play important roles in regulating secondary metabolism in many species, but less is known regarding black pepper or piperine biosynthesis. Results To dissect the functions of miRNAs in secondary metabolism especially in piperine biosynthesis, 110 known miRNAs, 18 novel miRNAs and 1007 individual targets were identified from different tissues of black pepper by small RNA sequencing. qRT-PCR and 5′-RLM-RACE experiments were conducted to validate the reliability of the sequencing data and predicted targets. We found 3 miRNAs along with their targets including miR166- 4CL , miR396 -PER and miR397- CCR modules that are involved in piperine biosynthesis. Conclusion MiRNA regulation of secondary metabolism is a common phenomenon in plants. Our study revealed new miRNAs that regulate piperine biosynthesis, which are special alkaloids in the piper genus, and they might be useful for future piperine genetic improvement of black pepper.

Objective: This study investigated the effects of dietary piperine (PIP) supplementation on feed efficiency, growth performance, digestive enzyme activity, hemolymph biochemistry, antioxidant and immune responses, and disease resistance in whiteleg shrimp (Litopenaeus vannamei) chal¬lenged with Vibrio parahemolyticus. Materials and Methods: A total of 320 shrimps (4.38 gm ± 0.2 gm) were randomly distributed into four treatments and fed a basal diet or supplemented with 0, 0.5 (PIP0.5), 1 (PIP1.0), and 2 (PIP2) gm/kg of diet. Results: The dietary inclusion of PIP significantly improved growth performance, blood proteins, and efficiency, resulting in the best results in the PIP2 group. Diets containing PIP led to significant improvements in crude protein and lipid content while also significantly reducing moisture con¬tent in a quadratic-dependent manner (p < 0.05). Shrimp in the PIP1 and PIP2 groups exhibited higher total protein and albumin levels compared to the free-PIP and PIP0.5 groups (p < 0.05). Shrimp-fed PIP-enriched diets showed lower lipid profiles (total cholesterol, triglycerides, and low-density lipoprotein) and liver enzymes (gam¬ma-glutamyl transferase and lactate dehydrogenase) in a quadratic trend (p < 0.05) compared to the control diet. Shrimp-fed diets containing PIPs exhibited a significant quadratic increase in digestive enzyme activity compared to those without PIPs (p < 0.05). The inclusion of PIP in the diet significantly enhanced antioxidant enzymes and reduced malondialdehyde levels, as well as the inflammatory response (Interleukin 4, Interferon-gamma, and LYZ) in shrimp. Conclusion: These findings suggest that dietary PIP supplementation holds promise as a feed additive for enhancing growth, immunity, and disease resistance in whiteleg shrimp.

Black pepper ( Piper nigrum ), dubbed the ‘King of Spices’ and ‘Black Gold’, is one of the most widely used spices. Here, we present its reference genome assembly by integrating PacBio, 10x Chromium, BioNano DLS optical mapping, and Hi-C mapping technologies. The 761.2 Mb sequences (45 scaffolds with an N50 of 29.8 Mb) are assembled into 26 pseudochromosomes. A phylogenomic analysis of representative plant genomes places magnoliids as sister to the monocots-eudicots clade and indicates that black pepper has diverged from the shared Laurales-Magnoliales lineage approximately 180 million years ago. Comparative genomic analyses reveal specific gene expansions in the glycosyltransferase, cytochrome P450, shikimate hydroxycinnamoyl transferase, lysine decarboxylase, and acyltransferase gene families. Comparative transcriptomic analyses disclose berry-specific upregulated expression in representative genes in each of these gene families. These data provide an evolutionary perspective and shed light on the metabolic processes relevant to the molecular basis of species-specific piperine biosynthesis. Black pepper ( Piper nigrum ) belongs to the long-isolated lineage of basal angiosperm and its fruit has been used for food spice and phytomedicines for thousands of years. Here, the authors assemble the reference genome of this species and analyze gene families associated with piperine biosynthesis.

Purpose Curcumin has shown to exert a positive impact on human glucose metabolism, even if its bioavailability is usually very low. The present study aimed to explore the effect of phosphatidylserine- and piperine-containing curcumin phytosomes on a large number of metabolic parameters related to insulin resistance, in the context of a randomized double-blind placebo-controlled trial involving 80 overweight subjects with suboptimal fasting plasma glucose. Methods Subjects were randomized to be treated with indistinguishable tablets (2 per day, to be taken after dinner) containing 800 mg phytosomal curcumin (Curserin®: 200 mg curcumin, 120 mg phosphatidylserine, 480 mg phosphatidylcholine and 8 mg piperine from Piper nigrum L. dry extract) for 8 weeks. Results After 56-day treatment, the curcumin-treated group experienced a significant improvement in fasting plasma insulin (FPI), HOMA index, waist circumference, blood pressure, triglycerides (TG), HDL-C, liver transaminases, gamma-GT, index of liver steatosis and serum cortisol compared to the baseline. FPI, TG, liver transaminases, fatty liver index and serum cortisol level also significantly improved compared with the placebo-treated group. Compared to the baseline, at the end of the study placebo group experienced an improvement only in FPG and TG. Conclusion In conclusion, the present trial shows that supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose.

Curcumin as the active compound of turmeric has antioxidative, antiinflammatory, antimicrobial and anticancer properties among others. However, its disadvantageous properties like low solubility, poor bioavailability and rapid degradation under neutral or alkaline pH conditions or when exposed to light limit its clinical application. These problems can be solved by a smart combination of using a natural enhancer like piperine and preparing nanoparticles by a proper method like electrospray.Due to these facts it was aimed in this study to develop curcumin and piperine loaded zein-chitosan nanoparticles step by step. For that purpose various formulation parameters like the concentrations of zein, curcumin, piperine and chitosan and the preparation parameters like the applied voltage and the nozzle diameter were investigated step by step. The nanoparticles were characterised by investigating their shapes, morphologies, particle sizes with help of SEM images and the cytotoxicity on neuroblastoma cells.It was succeeded to prepare curcumin and piperine loaded zein-chitosan nanoparticles having a mean particle size of approximately 500 nm and high encapsulation efficencies for curcumin (89%) and piperine (87%). Using a curcumin concentration of 10–25 µg/ml resulted in reduction of the viability of approximately 50% of the neuroblastoma cells. The here developed nanoparticle formulation consisting of solely natural compounds showed good cytotoxic effects and is a promising approach with appropriate properties for final consumption.