Pogostemon cablin (patchouli) cultivation is challenged by serious soil sickness, of which autotoxins accumulation is a major cause. p-hydroxybenzoic acid (p-HBA) is one of the main autotoxins of patchouli. However, the molecular mechanism underlying the response of patchouli to p-HBA remains unclear. In this study, RNA-sequencing combined with physiological analysis was used to monitor the dynamic transcriptomic and physiological changes in patchouli seedlings 0, 6, 12, 24, 48, and 96 h after p-HBA treatment. p-HBA stress inhibited root biomass accumulation, induced excessive hydrogen peroxide accumulation and lipid peroxidation, and activated most antioxidant enzymes. Compared with that of the control, the osmotic adjustment substance content was elevated with treatment. Subsequently, 15,532, 8,217, 8,946, 2,489, and 5,843 differentially expressed genes (DEGs) at 6, 12, 24, 48, and 96 h after p-HBA treatment, respectively, were identified in patchouli roots. GO functional enrichment analysis showed that the DEGs were enriched mainly in plasma membrane, defense response, response to chitin, DNA-binding transcription factor activity and abscisic acid-activated signaling pathway. The upregulated genes were involved in glycolysis/gluconeogenesis, cysteine and methionine metabolism, starch and sucrose metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. Genes associated with MAPK signaling pathway-plant, plant-pathogen interaction, plant hormone signal transduction were downregulated with p-HBA treatment. These pathways are related to root browning and rotting, leading to plant death.

Lung cancer is the leading cause of cancer-related deaths due to its high incidence, late diagnosis, and limited success in clinical treatment. Prevention therefore is critical to help improve lung cancer management. Although tobacco control and tobacco cessation are effective strategies for lung cancer prevention, the numbers of current and former smokers in the USA and globally are not expected to decrease significantly in the near future. Chemoprevention and interception are needed to help high-risk individuals reduce their lung cancer risk or delay lung cancer development. This article will review the epidemiological data, pre-clinical animal data, and limited clinical data that support the potential of kava in reducing human lung cancer risk via its holistic polypharmacological effects. To facilitate its future clinical translation, advanced knowledge is needed with respect to its mechanisms of action and the development of mechanism-based non-invasive biomarkers in addition to safety and efficacy in more clinically relevant animal models.

4-(Methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its major metabolite 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are tobacco-specific lung carcinogens. NNK is widely used in preclinical models to induce lung tumorigenesis for elucidating carcinogenesis mechanisms and developing preventive agents, because of the high tumour burden in a cost-effective manner. Typical NNK doses employed in these models substantially exceed levels in humans and the routes of administration (e.g. intraperitoneal injection, oral gavage, or delivery via drinking water) differ fundamentally from inhalational exposure through cigarette smoke. At the molecular level, NNK and NNAL undergo metabolic bioactivation by cytochrome P450 enzymes, generating reactive intermediates capable of covalently modifying DNA and proteins, thereby initiating carcinogenesis. NNK and NNAL are also subject to competing metabolism. Their portion undergoing carcinogenic bioactivation is expected to vary as a function of dose and route of exposure, raising concerns about the physiological relevance of these preclinical models. Systematic comparison of NNK and NNAL bioactivation profiles in humans with these preclinical models can help assess their physiological relevance and inform translational application. Using LC–MS/MS methods, this study quantified 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB, an NNK-derived bioactivation hydrolysis product) and 1-(3-pyridyl)-1,4-butanediol (PBD, an NNAL-specific bioactivation hydrolysis product) in lung, liver, and serum samples from two mouse models and in human lung and plasma samples. Marketed differences were observed between NNK intraperitoneal preclinical models and human samples; in contrast, the tobacco smoke-based preclinical model better recapitulates human NNK and NNAL bioactivation. These results provide guidance for the future use of these models in investigating lung carcinogenesis and developing preventive agents.