The potential role of Piper guineense (black pepper) in managing geriatric brain aging: a review

Figures & data

Figure 1. Paths of brain aging (Adapted from Mattson and Arumugam 2018; UCDavis).

Figure 2. Hypothesis for the pathophysiology of Alzheimer’s disease (Adapted from Kumar Thakur et al. 2018).

Figure 3. Schematic diagram showing the different factors in play in the pathophysiology of Parkinson’s disease (Adapted from Farooqui and Farooqui 2011).

Figure 4. (a). P. guineense fresh leaves, ripened bunches of fruits and dried fruits (black pepper) (Imo et al. 2018; Oyemitan, Kolawole, and Oyedeji 2014). (b) Structure of piperine and other naturally occurring phytochemicals in P. guineense.

Table 1. Phytochemical compounds and extracted piperine content of Piper spp.

Piper spp. (plant part)	Compounds		Analytical instrument	References
Piper guineense (fresh leaves)	Flavonoid, alkaloid, saponin, tannin, and phenol		Spectrophotometry	(Amadioha and Chidi 2019)
Piper spp. (fruits)	Piperamides (such as Piperolactam C, Piperlongumine, Piperyline, Piperanine, Piperine, Piperdardine, Piperettines, Pellitorine, Pipercallosine, Neopellitorine B, Guineensine, Piperchabamide C, and so on)		LC-DAD	(Luca et al. 2021)
Piper guineense (leaves)	Piperine, Piperidine		GC-MS	(Sulaimon et al. 2020)
Piper guineense and Piper umbellatum Linn. (leaves and stem)	Alkaloids, saponins, flavonoids, phenolics, tannins		Spectrophotometry	(Isikhuemen, Ogbomwan, and Efenudu 2020)
Piper nigrum L. pericap	Flavonoids, phenolics, monoterpene, primary sesquiterpenes		Spectrophotometry	(Lee et al. 2020)
Piper spp. (plant part)	Recovered amount of piperine		Analytical instrument	Reference
P. nigrum (black and white fruits)	2.5–4.5 %		HPLC	(Rahman Khan et al. 2017)
P. nigrum (pericarp)	2352.19 mg/100 g		HPLC	(Lee et al. 2020)
P. retrofractum (fruit)	19.1–18.5 %		HPLC	(Cahyono et al. 2019)
P. nigrum (fruit)	90.14–96.15 %		Spectrophotometry	(Raman and Gaikar 2002)
P. borbonense, P. nigrum, P. guineense, P. cubeba and P. longum	1.01–274.86 mg/g		LC-DAD	(Luca et al. 2021)

*GC-MS, Gas chromatography mass spectrometry; HPLC, High performance liquid chromatography; LC-DAD, liquid chromatography–diode array detector.

Table 2. Neuroprotective potential of some components of Piper guineense.

Compounds in P. guineense	Functional role in brain health	Mechanisms	References
Piperine	Anti-depressant (ameliorate chronic mild stress) Neuroprotection (improve motor coordination and balance behavior) Anti-inflammatory (control inflammatory biomarkers) Anti-apoptosis Enhance cholinergic activity	Upregulate progenitor cell proliferation of hippocampus and cytoprotective activities; reduce in serum levels of adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) Reduce production of TBARS Inhibit the production of cytokines following the inhibition of microglial activation in 6-OHDA induced PD. Inhibit the activation of apoptosis by inhibiting the execution of caspase-9 and caspase-3. Increase acetylcholine by preventing the accumulation of β-amyloid or inhibiting the AChE and tangle contents in the brain tissues.	(Li et al. 2007); (Hu et al. 2009) (Butt et al. 2013) (Butt et al. 2013) (Shrivastava et al. 2013) (Shrivastava et al. 2013)
Antioxidant	Neuroprotection (improve brain function)	Reduce production of TBARS, lipid peroxidation, and protein oxidation. Inhibit β-amyloid self-induced aggregation	(Yusuf et al. 2013)(Butt et al. 2013) (Hritcu et al. 2015) (Tu et al. 2016)
Essential oil	Anti-depressant Mild tranquilizer (relieve anxiety)	Interact with the serotonergic route through post-synaptic 5- 16HT1A receptors and the adrenergic system through α2-receptors. Inhibit glutamatergic transmission in the central nervous system	(dos Santos et al. 2018) (Tankam and Ito 2013)

Mattson, M. P., and T. V. Arumugam. 2018. Hallmarks of brain aging: Adaptive and pathological modification by metabolic states. Cell Metabolism 27 (6):1176–99. doi: 10.1016/j.cmet.2018.05.011.

 PubMed Web of Science ®Google Scholar

Kumar Thakur, A., P. Kamboj, K. Goswami, and K. Ahuja. 2018. Pathophysiology and management of Alzheimer’s disease: An overview. Journal of Analytical & Pharmaceutical Research 7 (2):226–35. doi: 10.15406/japlr.2018.07.00230.

 Google Scholar

Farooqui, T., and A. A. Farooqui. 2011. Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson’s disease. Parkinson’s Disease 2011:247467. doi: 10.4061/2011/247467.

 PubMed Web of Science ®Google Scholar

Imo, C., O. E. Yakubu, N. G. Imo, I. S. Udegbun, S. V. Tatah, and O. J. Onukwug. 2018. Proximate, mineral and phytochemical composition of Piper guineense seeds and leaves. Journal of Biological Sciences 18 (7):329–37. doi: 10.3923/jbs.2018.329.337.

 Google Scholar

Oyemitan, I. A., F. Kolawole, and A. O. Oyedeji. 2014. Acute toxicity, antinociceptive and anti-inflammatory activity of the essential oil of fresh fruits of Piper guineense Schum Thonn (Piperaceae) in rodents. Journal of Medicinal Plants Research 8 (40):1191–7. doi: 10.5897/JMPR2014.5639.

 Google Scholar

Amadioha, A. C., and K. P. Chidi. 2019. Phytochemical Composition of aqueous and ethanolic leaf extracts of Piper guineense, Cassia alata, Tagetes erecta and Ocimum graticimum. Journal of Pharmaceutical Research International 26 (3):1–8. doi: 10.9734/jpri/2019/v26i330136.

 Web of Science ®Google Scholar

Luca, S. V., M. Minceva, J. Gertsch, and K. Skalicka-Woźniak. 2021. LC-HRMS/MS-based phytochemical profiling of Piper spices: Global association of piperamides with endocannabinoid system modulation. Food Research International (Ottawa, Ont.) 141:110123. doi: 10.1016/j.foodres.2021.110123.

 PubMed Web of Science ®Google Scholar

Sulaimon, L. A., E. O. Anise, E. M. Obuotor, T. A. Samuel, A. I. Moshood, M. Olajide, and T. Fatoke. 2020. In vitro antidiabetic potentials, antioxidant activities and phytochemical profile of african black pepper (Piper guineense). Clinical Phytoscience 6 (1):1–13. doi: 10.1186/s40816-020-00236-2.

 Google Scholar

Isikhuemen, E. M., B. O. Ogbomwan, and I. U. Efenudu. 2020. Evaluation of phytochemical and mineral constituents of Piper guineense Schum. and Thonn. and Piper umbellatum Linn: Implications for ethnomedicine. European Journal of Medicinal Plants 31 (1):84–97. doi: 10.9734/ejmp/2020/v31i130209.

 Google Scholar

Lee, J. G., Y. Chae, Y. Shin, and Y. J. Kim. 2020. Chemical composition and antioxidant capacity of black pepper pericarp. Applied Biological Chemistry 63 (1):1–9. doi: 10.1186/s13765-020-00521-1.

 Web of Science ®Google Scholar

Rahman Khan, Z., F. Moni, S. Sharmin, M. A. Al-Mansur, A. Gafur, O. Rahman, and F. Afroz. 2017. Isolation of bulk amount of piperine as active pharmaceutical ingredient (API) from black pepper and white pepper (Piper nigrumand L.). Pharmacology & Pharmacy 08 (07):253–62. doi: 10.4236/pp.2017.87018.

 Google Scholar

Cahyono, B., Hasanah, E. F. Judiono, Suzery, and M. Widayat. 2019. Analysis of piperine content in cabe jawa extracts (Piper retrofractum Vahl) using UV spectrophotometry and HPLC. IOP Conference Series: Materials Science and Engineering 509 (012025):1–5. doi: 10.1088/1757-899X/509/1/012025.

 Google Scholar

Raman, G., and V. G. Gaikar. 2002. Extraction of Piperine from Piper nigrum (Black Pepper) by Hydrotropic Solubilization. Industrial & Engineering Chemistry Research. 41 (12):2966–76. doi: 10.1021/ie0107845.

 Web of Science ®Google Scholar

Li, S., C. Wang, M. Wang, W. Li, K. Matsumoto, and Y. Tang. 2007. Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms . Life Sciences 80 (15):1373–81. doi: 10.1016/j.lfs.2006.12.027.

 PubMed Web of Science ®Google Scholar

Hu, Y., H. B. Liao, P. Liu, D. H. Guo, and Y. Y. Wang. 2009. [Antidepressant effects of piperine and its neuroprotective mechanism in rats] . Zhong xi yi Jie he Xue Bao = Journal of Chinese Integrative Medicine 7 (7):667–70. doi: 10.3736/jcim20090712.

 PubMedGoogle Scholar

Butt, M. S., I. Pasha, M. T. Sultan, M. A. Randhawa, F. Saeed, and W. Ahmed. 2013. Black pepper and health claims: A comprehensive treatise. Critical Reviews in Food Science and Nutrition 53 (9):875–86. doi: 10.1080/10408398.2011.571799.

 PubMed Web of Science ®Google Scholar

Shrivastava, P., K. Vaibhav, R. Tabassum, A. Khan, T. Ishrat, M. M. Khan, A. Ahmad, F. Islam, M. M. Safhi, and F. Islam. 2013. Anti-apoptotic and anti-inflammatory effect of piperine on 6-OHDA induced Parkinson’s rat model. Journal of Nutritional Biochemistry 24 (4):680–87. doi: 10.1016/j.jnutbio.2012.03.018.

 PubMed Web of Science ®Google Scholar

Yusuf, M., M. Khan, R. A. Khan, and B. Ahmed. 2013. Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s disease model. Journal of Drug Targeting 21 (3):300–11. doi: 10.3109/1061186X.2012.747529.

 PubMed Web of Science ®Google Scholar

Hritcu, L., J. A. Noumedem, O. Cioanca, M. Hancianu, P. Postu, and M. Mihasan. 2015. Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer’s disease . Behavioral and Brain Functions: BBF 11 (1):13. doi: 10.1186/s12993-015-0059-7.

 PubMedGoogle Scholar

Tu, Y., Y. Zhong, H. Du, W. Luo, Y. Wen, Q. Li, C. Zhu, and Y. Li. 2016. Anticholinesterases and antioxidant alkamides from Piper nigrum fruits. Natural Product Research 30 (17):1945–9. doi: 10.1080/14786419.2015.1089243.

 PubMed Web of Science ®Google Scholar

dos Santos, É. R. Q., C. S. F. Maia, E. A. Fontes Junior, A. S. Melo, B. G. Pinheiro, and J. G. S. Maia. 2018. Linalool-rich essential oils from the Amazon display antidepressant-type effect in rodents. Journal of Ethnopharmacology 212:43–9. doi: 10.1016/j.jep.2017.10.013.

 PubMed Web of Science ®Google Scholar

Tankam, J. M., and M. Ito. 2013. Inhalation of the essential oil of Piper guineense from Cameroon shows sedative and anxiolytic-like effects in mice. Biological & Pharmaceutical Bulletin 36 (10):1608–14. doi: 10.1248/bpb.b13-00491.

 PubMed Web of Science ®Google Scholar