Monocyclic monoterpenes have been recognized as useful pharmacological ingredients due to their ability to treat numerous diseases. Limonene and perillyl alcohol as well as their metabolites (especially perillic acid and its methyl ester) possess bioactivities such as antitumor, antiviral, anti-inflammatory, and antibacterial agents. These therapeutic properties have been well documented. Based on the aforementioned biological properties of limonene and its metabolites, their structural modification and development into effective drugs could be rewarding. However, utilization of these monocyclic monoterpenes as scaffolds for the design and developments of more effective chemoprotective agents has not received the needed attention by medicinal scientists. Recently, some derivatives of limonene metabolites have been synthesized. Nonetheless, there have been no thorough studies on their pharmacokinetic and pharmacodynamic properties as well as their inhibition against isoprenylation enzymes. In this review, recent research progress in the biochemical significance of limonene and its metabolites was summarized with emphasis on their antitumor effects. Future prospects of these bioactive monoterpenes for drug design and development are also highlighted.

Punicic acid of pomegranate oil (PAP) has gained heightened interest due to several health benefits, such as anticarcinogenic, antidiabetic, and antiatherosclerotic properties. However, these bioactivities have been hampered by chemical instability, poor water solubility, rapid metabolism, and low bioavailability of PAP. Therefore, this study was aimed at optimizing the liposomal formulation of Triacylglycerol‐bound punicic acid with its regioisomers (TPAR) for improved oral bioavailability and increased hepatoprotection through antioxidation and anti‐inflammation. Herein, the optimized TPAR nanoliposome (TPAR‐NL) was developed using thin‐film dispersion method and subsequently characterized with appropriate indices. The optimized TPAR‐NL produced fairly stable spherical nanoparticles (˂ 200 nm) with encapsulation efficiency (%EE) of 85.77%, as well as enhanced in vitro release and improved oral bioavailability. The TPAR‐NL exhibited profound antihepatotoxic effect in mice pretreated with carbon tetrachloride (CCl4) via reduction of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels compared with free TPAR. The TPAR‐loaded liposome also significantly reduced oxidative stress by increasing superoxide dismutase and glutathione levels while lowering malonaldehyde concentration compared with the free TPAR. The TPAR‐LNF further exhibited remarkable anti‐inflammatory activity compared with the free drug via inhibition of interleukin‐6 and tumor necrosis factor‐alpha generation. Thus, the developed nanoliposomes potentiated the antihepatotoxic activity of TPAR via antioxidation and anti‐inflammation.

Objectives Cuminaldehyde self‐emulsified nanoemulsion (CuA‐SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. Methods Cuminaldehyde self‐emulsified nanoemulsion was developed through the self‐nanoemulsification method using Box–Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA‐SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in‐vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. Key findings Cuminaldehyde self‐emulsified nanoemulsion with acceptable characteristics (mean DS‐48.83 ± 1.06 nm; PDI‐0.232 ± 0.140; ZP‐29.92 ± 1.66 mV; EE‐91.51 ± 0.44%; and drug‐loading capacity (DL)‐9.77 ± 0.75%) was formulated. In‐vitro drug release of CuA‐SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA‐SEN to CCl4‐induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA‐SEN reduced the levels of tumour necrosis factor‐alpha and interleukin‐6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. Conclusions These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti‐inflammation and antihepatotoxicity of the drug.

Emerging evidence has suggested that nutraceutical ingredients like pomegranate seed oil (PSO) possesses health‐promoting effects in cell and animal models. However, these health benefits (anticancer, antioxidant, anti‐inflammatory, anti‐diabetic, and so on) are limited by low physicochemical stability, slow intestinal absorption, and rapid metabolism of PSO. In order to overcome these drawbacks, some carriers viz., nanoemulsion, encapsulation, and nanoparticles are developed recently. This paper assesses the chemical compositions and physicochemical properties of PSO, as well as biological activities and possible mechanisms. It also discusses the formulation of PSO for improved stability and health‐promoting activities. Practical Applications: This review highlights the prospects of PSO formulation. The relevance of this study is that the stability and biological properties of PSO could be enhanced through nanocarriers. A formulated PSO has a potential use in nutraceutical, functional foods, pharmaceutical and cosmetic industries. PSO, a source of various nutrients and antioxidants with immense benefits to human health is incorporated into nanocarriers such as microencapsulation, nanoemulsion and nanoparticle. This improved the health‐promoting benefits of the oil.

(S)-Perillic acid derivatives bearing N-aryl moiety with enhanced cytotoxic and antitumor effect against hepatocellular carcinoma and glioblastoma.