Oral Administration of Nicotinamide Mononucleotide with Bioenhancer BioPerine® Increases the Serum Concentration of Nicotinamide Adenine Dinucleotide in Healthy Human Volunteers: A Pilot, Open-Label, Cross-Over Study

Background: Bioenhancers augment the bioavailability of co-administered molecules without showing any significant effect on their own. Piperine, an alkaloid from Piper nigrum, is an established natural bioenhancer. Nicotinamide mononucleotide (NMN), an antiaging supplement, is the precursor of coenzyme nicotinamide adenine dinucleotide (NAD) that plays an important role in intracellular redox reactions. Objective: The study compared the serum concentrations of NAD in normal healthy participants, supplemented with NMN 500 mg and NMN 500 mg + 5 mg BioPerine® (95% piperine). Methods: In a randomized, open-label, crossover study, NMN (500 mg) was compared to NMN + BioPerine® (500 mg + 5 mg) in 6 healthy adults, aged 18 - 45 years. The participants received a single oral dose of NMN or NMN + BioPerine® capsules with 240 mL water, and blood samples were collected over 8hr. After a 4-day washout period, the same procedures were repeated as per the crossover design. Total NAD (NADtotal), including oxidized NAD (the oxidized) and its reduced form NADH, was measured in human serum samples. Results: The maximum concentration (Cmax) of NAD in serum was higher with NMN + BioPerine® (282 pmol/mL) compared to NMN (246 pmol/mL) alone. In the presence of BioPerine®, the NAD concentrations reached 257 pmol/mL during the first 2 hr, whereas a comparable serum concentration (246 pmol/mL) was attained only after 6 hr in NMN alone. The AUC0-8hr was 1738 pmol/mL/hr in NMN compared to 2004 pmol/mL/hr in NMN+ BioPerine®. The time to reach peak concentration (t1/2) was similar (6hr) in both groups. No clinically relevant adverse events (AE) were observed, and safety parameters remained within normal ranges in all the participants with both formulations. Conclusion: These results reveal that BioPerine® can effectively increase the NAD concentrations in the serum following NMN supplementation in healthy volunteers. The present study was registered prospectively with the Clinical Trials Registry-India (CTRI/2023/11/059982).

BioPerine Encapsulated Nanoformulation for Overcoming Drug-Resistant Breast Cancers

The evolving dynamics of drug resistance due to tumor heterogeneity often creates impediments to traditional therapies making it a challenging issue for cancer cure.Breast cancer often faces challenges of current therapeutic interventions owing to its multiple complexities and high drug resistivity,for example against drugs like trastuzumab and tamoxifen.Drug resistance in the majority of breast cancer is often aided by the overtly expressed P-glycoprotein(P-gp)that guides in the rapid drug efflux of chemotherapy drugs.Despite continuous endeavors and ground-breaking achievements in the pursuit of finding better cancer therapeutic avenues,drug resistance is still a menace to hold back.Among newer therapeutic approaches,the application of phytonutrients such as alkaloids to suppress P-gp activity in drug-resistant cancers has found an exciting niche in the arena of alternative cancer therapies.In this work,we would like to present a black pepper alkaloid derivative known as Bio Perine-loaded chitosan(CS)-polyethylene glycol(PEG)coated polylactic acid(PLA)hybrid polymeric nanoparticle to improve the bioavailability of Bio Perine and its therapeutic efficacy in suppressing P-gp expression in MDA-MB 453 breast cancer cell line.Our findings revealed that the CS-PEG-Bio PerinePLA nanoparticles demonstrated a smooth spherical morphology with an average size of316 nm,with improved aqueous solubility,and provided sustained Bio Perine release.The nanoparticles also enhanced in vitro cytotoxicity and downregulation of P-gp expression in MDA-MB 453 cells compared to the commercial inhibitor verapamil hydrochloride,thus promising a piece of exciting evidence for the development of Bio Perine based nano-drug delivery system in combination with traditional therapies as a crucial approach to tackling multi-drug resistance in cancers.