Benzoylaconine (Isaconitine; Pikraconitin) is an alkaloid in the Chinese traditional medicine Radix Aconiti Lateralis Preparata (Fuzi). Benzoylaconine is a metabolite of aconitine. Benzoylaconine increased P-gp expression in LS174T and Caco-2 cells, it also increased the P-gp transport activity. Benzoylaconine has being shown to stimulate dynorphin A expression in cultured primary spinal microglia.

Roquefortine C, a cyclopeptide derived from the diketopiperazine cyclo(Trp-dehydroHis), is a secondary metabolite produced by several Penicillium species, especially by Penicillium roqueforti, which is used as starter culture for blue cheese production. Although roquefortine C is frequently detected in the products, it obviously has an insignificant toxicity to humans after ingestion. However, intoxications in dogs and cattle have been reported. Its bacteriostatic activities against Gram-positive bacteria lead to Roquefortine C potential use in antibiotics, but its development as a drug has been stopped due to its neurotoxic effects in mice. Roquefortine C activates P-gp and inhibits P450-3A and other haemoproteins. Roquefortine C can serve as a sensitive biomarker for penitrem A intoxication.

Schisantherin A is a dibenzocyclooctadiene originally found in Schisandra that exhibits anti-tussive, sedative, anti-inflammatory, anti-osteoporotic, neuroprotective, cognition enhancing, and cardioprotective activities. In macrophages, schisantherin A decreases LPS-induced expression and activity of iNOS, COX-2, NO, IL-6, and TNF-α. Schisantherin A also decreases RANKL-induced NF-κB signaling by inhibiting IκBα degradation and suppressing JNK and ERK1/2 activation in vitro; it also inhibits osteoclast function and bone erosion in vivo. In animal models of Alzheimer’s disease, schisantherin A inhibits amyloid-β (Aβ)-induced learning and memory impairments in Y maze, shuttle box, and Morris water maze assays. Additionally, this compound lowers left ventricular systolic and end diastolic pressures, decreases infarct size and maldionaldehyde release, and increases superoxide dismutase activity, preventing myocardial apoptosis in animal models of cardiac ischemia/reperfusion. Schisantherin A conferred significant protection against MPTP-induced loss of TH-positive dopaminergic neurons in a Parkinson's disease (PD) mice model. Western blotting analysis demonstrated that Schisantherin A exhibited neuroprotection against MPP(+) through the regulation of two distinct pathways including increasing CREB-mediated Bcl-2 expression and activating PI3K/Akt survival signaling suggesting that StA might be a promising neuroprotective agent for the prevention of PD.

11-NOR-9-CARBOXY-DELTA9-TETRAHYDROCANNABINOL (THC-COOH) is the main the non-psychoactive metabolite of Delta9-Tetrahydrocannabinol. Being most abundant in bodily fluids, it has become an established marker of cannabis consumption in forensic, clinical and environmental analyses. Among the cannabinoids tested as potential inhibitors of the drug efflux transporter P-glycoprotein (Pgp), which is responsible for the multidrug-resistance of a tumour and normal cells, THC-COOH behaved as a substrate and was the most active in stimulating Pgp-dependent ATPase. It displayed analgesic and anti-inflammatory properties apparently by inhibiting cyclooxygenase and 5-lipoxygenase activities. THC-COOH was not an anxiolytic or anxiogenic drug but abolished the anxiogenic behavioral effect of Delta9-Tetrahydrocannabinol.

Digitonin is a steroidal saponin (saraponin) obtained from the foxglove plant Digitalis purpurea. As a non-ionic detergent Digitonin is commonly used to solubilize membrane-bound proteins. Digitonin forms a complex with its lipophilic terpenoid moiety with cholesterol in the biomembrane; additionally it binds to glycoproteins and glycolipids of the cell membrane with its sugar side chain. This leads to a severe tension of the biomembrane and influences membrane permeability. Digitonin, in combination with secondary metabolites, leads to a stronger inhibition of ABC transporters as when applied alone. Digitonin is used as a clinical reagent for the cholesterol determination. Digitonin mixed in the diet was well tolerated by rats and cynomolgus monkeys (Macaca fascicularis), and prevented the expected rise in plasma cholesterol in monkeys fed a diet containing butter and cholesterol.

Cinchonine is cinchona bark alkaloid, which was used to treat malaria. Cinchonine is more efficient than quinine in increasing the intracellular accumulation and restoring the cytotoxicity of doxorubicin, mitoxantrone and vincristine on well-characterized multidrug resistance (MDR) cell lines. In the phase I of clinical trial was investigated the properties of cinchonine combined with the CHVP (cyclophosphamide, doxorubicin, vinblastine, methylprednisolone) regimen in relapsed and refractory lymphoproliferative syndromes.

Emetine is a principal alkaloid of ipecac, isolated from the ground roots of Uragoga ipecacuanha. Early use of emetine was in the form of oral administration of the extract of ipecac root, or ipecacuanha. This extract contains several, including cephaeline, and others. The identification of emetine as a more potent agent improved the treatment of amoebiasis. While the use of emetine still caused nausea, it was more effective than the crude extract of ipecac root. Additionally, emetine could be administered hypodermically which still produced nausea, but not to the degree experienced in oral administration. Emetine dihydrochloride hydrate is used in the laboratory to block protein synthesis in eukaryotic cells. It does this by binding to the 40S subunit of the ribosome. Emetine induces hypotension by blocking adrenoreceptors. Also, emetine was identified as a specific inhibitor of HIF-2α protein stability and transcriptional activity. Heavy or over usage of emetine can carry the risk of developing proximal myopathy and/or cardiomyopathy.

Bifendate is a synthetic intermediate of Schisandrin C and also an anti-HBV drug used in Chinese medicine for the treatment of chronic hepatitis B. Following the intake of Bifendate in rats, the drug was observed to improve liver function by increasing the detoxification process, reducing pathological lesions, and accelerating hepatocyte regeneration. Bifendate can also function as a membrane-stabilizing agent to protect the cell from damage. After treatment with Bifendate, the protein metabolic processes of hepatitis patients were improved, with increased serum albumin levels and decreased globulin levels. Bifendate is a potent inducer of cytochrome proteins (CYPs) and can result in clinically significant interactions. It has been proposed that the increased detoxification capability of Bifendate originates from an increase in the level of P450. Bifendate may function as a protecting agent to prevent drug-induced liver dysfunction by increasing the activity of CYP450.