Supercritical Carbon Dioxide (SC-CO2 ) Extraction of Piperine: A Green Extraction Method for Biomolecule of Therapeutic Importance


Black pepper is a popular condiment globally. The bioactive principle compound of this is spice is piperine, which is a biomolecule of immense nutraceutical significance. This chapter elaborates on various green technologies of extraction of the active constituent, piperine from black pepper. Green technology of supercritical carbon dioxide (SC-CO,) extraction has particularly been emphasized upon. Various engineering process parameters influencing the yields of piperine in the SC-CO, extracts, such as assessment of piperine solubility in SC-CO,; mass transfer and packed bed characteristics, and kinetics of piperine release from the black pepper matrix during extraction have been critically discussed. The SC-CO, extracts of piperine can be safely utilized as food and therapeutic supplements.


Spices are used extensively in the current era of drugs for the formulation of dietary supplements and natural medicines to alleviate ailments with success (Vaidya and Devasagayam, 2007). The bioactive components of spices which confers the medical (treatment of disease) or health (prevention of diseases) benefits are known as ‘spiceuticals.’ For use as food or therapeutic supplements (drugs), these spiceuticals should preferably be natural or at least nature-identical to avoid bio-incompatibility and other undesirable side effects. Consequently, there is a need to obtain extracts of the spiceuticals from their native natural resources in forms completely safe for human consumption and with unaltered therapeutic potencies as are in their natural forms (Mukhopadhyay, 2000). Conventional methods for extraction of these bioactive components are cumbersome, time-consuming, and involve organic solvents for extraction. The extracts obtained by these techniques necessitate downstream processing since they contain residual solvents (toxic), artifacts, and undesirable co-extracted components along with the desired biomolecule. Hence, these extracts are not safe for food and therapeutic applications (Mukhopadhyay, 2000). ‘Green technologies’ of extraction of spiceuticals are therefore gaining importance since they comply with global regulations of safety for health and environment, bypass downstream processing and provide application- ready safe extracts.

Black pepper is known as the ‘Kang of Spices’ since globally it is the most important commercial spice, widely acclaimed for its characteristic pungency and confers therapeutic benefits provided by its spiceutical ‘piperine.’ Pipeline exhibits a wide range of bio-protective functionalities such as anti-inflammatory, neuro-protective, and cardio-protective effects. It also increases the bioavail- ability of several drugs and nutrients (Doucette et al., 2013). Considering the therapeutic properties of piperine, there is a need to explore this biomolecule as a potential biotherapeutic supplement in food and medicine.


Piperine (C17HI9N03, l-[5-(l,3-Benzodioxol-5-yl)-l-oxo-2,4-pentadienyl]-, (f.F'l-piperidine) is an alkaloid and is the principal bioactive compound of black pepper present in its oleoresin. Figure 5.1 shows the molecular structure of piperine. Piperine also occurs in the fruit of Aschanti (P. clusii C.) and in the kernel of ripe white pepper (Piper nigrum). It is also found in long pepper (.P longum L.) and in the seeds of P lowong (Table 5.1) (Manske and Holmes, 2014). It was first isolated from black pepper in 1920 by a Danish chemist Hans Christian Orstedt (Butt et al., 2013). It is a crystalline substance (yellow in color) which melts in the temperature range of 128-130°C (McNamara et al., 2005) and is responsible for the characteristic pungency of black (Piper nigrum L.) and long pepper (Piper longum L.) (Singh et al., 2004). Table 5.1 lists various sources of this spiceutical.

Molecular structure of piperine

FIGURE 5.1 Molecular structure of piperine.

TABLE 5.1 Sources of Piperine

Source of Piperine

Pipeline Content (%)

Aschanti (P. clusii C.)


Black pepper (Piper nigrum)


Long pepper (P. longum L.)


P lowong


It is evident from Table 5.1 that black pepper constitutes the maximum amount of piperine. The diverse physiological effects of black pepper and its active constituent piperine have been illustrated in Figure 5.2. Although research corroborates the efficacy of piperine as a biotherapeutic molecule, extensive applications of the same in food and in medicine are limited. In medicines, piperine acts as bioenliancer by increasing the bioavailability of nutritive substances such as (3-carotene (Singh et al., 2004; Hu et al., 2005). It also enhances the bioavailability of several drugs, namely rifampicin, ampicillin, and diclofenac sodium by increasing their absorption in the blood (Pooja et al., 2007; Chawla, 2010; Randhawa et al., 2011). In a study on the medicinal properties of piperine, Grinevicius et al. (2017) suggested that piperine can contribute to anti-cancer therapy. The bioconversion pathways piperine in rat models has been illustrated in Figure 5.3 (Srinivasan, 2007). There is evidence in support of piperine as a nutraceutical and food preservative. In food processing, piperine has been successfully utilized as a natural flavorant as well as an antimicrobial (preservative) in meat (pork) and allied products (Tipsrisukond et al., 1998). Pipeline extract is also reportedly known to limit oxidative rancidity in drop cookies (Dutta et al., 2017). These benefits of pipeline in black pepper extracts can be explored when extracted using safe green technologies of extraction.

Physiological effects of piperine and black pepper

FIGURE 5.2 Physiological effects of piperine and black pepper.

Source: Reprinted with permission from Srinivasan (2007). © Taylor & Francis.

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