A Botanical Drug Extracted From Antrodia cinnamomea: A First-in-human Phase I Study in Healthy Volunteers.

LEAC-102 is an emerging drug extracted from the medicinal fungus Antrodia cinnamomea (AC), which is traditionally used to ameliorate fatigue and liver disorders arising from excessive alcohol consumption. AC has been used as a health product with an immunomodulatory function, but its anticancer effect has not been applied in clinical therapy as a drug. This first-in-human study examined the safety and tolerability of LEAC-102 as a new drug in healthy adults.This standard 3 + 3 dose-escalation study included 18 participants administered LEAC-102 at doses of 597.6, 1195.2, 1792.8, 2390.4, or 2988 mg/day for 1 month plus 7 days of safety follow-up. The maximum planned dose was 2988 mg. Dose-limiting toxicity (DLT) was monitored from the start of LEAC-102 administration up to the final visit. The dose of LEAC-102 was escalated to the subsequent cohort as long as there was no DLT in the previous cohort. Tolerability, clinical status, safety (by laboratory parameters), and adverse event occurrence were documented weekly during the treatment and 1 week after the conclusion of the treatment.All clinical biochemistry profiles were in the normal range, and no serious adverse effects were observed. The maximum tolerated dose of LEAC-102 was determined to be 2988 mg/day because one participant experienced urticaria. Additionally, our exploratory objectives revealed that LEAC-102 significantly elevated natural killer, natural killer T, and dendritic cells in a dose-dependent manner, activated effector T cells, and upregulated programmed cell death-1 expression.The outcomes suggested that LEAC-102 was well tolerated and safe in healthy adults and exhibited potential immunomodulatory function.Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2022.2032868 .

Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mouse mammary tumor metastasis.

Dendritic cell (DC) vaccines are a newly emerging immunotherapeutic approach for the treatment and prevention of cancer, but major challenges still remain particularly with respect to clinical efficacy. Engineering and optimization of adjuvant formulations for DC-based vaccines is one strategy through which more efficacious treatments may be obtained. In this study, we developed a new ex vivo approach for DC vaccine preparation. We evaluated two highly purified mixed polysaccharide fractions from the root of Astragalus membranaceus and Codonopsis pilosulae, named Am and Cp, for their use in enhancing the efficiency of a DC-based cancer vaccine against metastasis of 4T1 mammary carcinoma in mice. Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation. [Am+Cp]-treated DCs exhibited the strongest anti-4T1 metastasis activity in test mice. Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs. Bioinformatics analysis of the cytokine array data from treated DCs identified that [Am+Cp] is efficacious in activation of specific immune functions via mediating the expression of cytokines/chemokines involved in the recruitment and differentiation of defined immune cells. Biochemical analysis revealed that Am and Cp are composed mainly of polysaccharides containing a high level (70-95%) glucose residues, but few or no (< 1%) mannose residues. In summary, our findings suggest that the specific plant polysaccharides Am and Cp extracted from traditional Chinese medicines can be effectively used instead of bacterial LPS as a potent adjuvant in the formulation of a DC-based vaccine for cancer immunotherapies.

Effect of Tianma Gouteng Decoction with subtractive ingredients and its active constituents on memory acquisition.

Accumulating evidence indicates that the high blood pressure (BP) is a potent risk factor for dementia in the elderly. In line with this theory, we had found the mixture of Chinese herbs (TGD) which were traditionally used to treat hypertension, could enhance the cognitive function. The aim of this study was to decrease the number of herbs used from 11 (TGD) to 4 herbs (TGDS) and further to search the active constituents. After administering a dose of 10 g/kg of TGDS0 to ICR mice, no cholinergic symptoms of lacrimation, salivation, emesis, eyeclosure, increased respiration and fibrillation were observed. All the mice survived without any deaths after 24 hours and 7 days. No changes were observed in control and experimental groups on locomotor activity (no stimulant or sedative effects). It was also revealed that TGDS could prolong the step-through latency at the dose of 1.0 and 2.5 g/kg on passive avoidance tasks in mice. This result was the same as the previous study. The active constituents which enhanced the memory acquisition were discovered in the butanol layer and ethyl acetate layer after the extraction.

Traditional Chinese herbs against hypertension enhance memory acquisition.

Recent findings of a link between high blood pressure (BP) and dementia have given new prospects. The aim of this study is to analyze a mixture of Chinese herbs, Tianma Gouteng Decoction (TGD), which was traditionally used to treat hypertension, and investigate its relation to ameliorating cognitive impairment. We discovered that TGD also had properties involving enhancement of memory acquisition (learning) skills in mice, but not memory consolidation. It was observed that TGD could prolong the step-through latency at doses of 1.0 and 2.5 g/kg on passive avoidance task in mice. TGD could be developed further to treat mice with amnesia, which was induced by scopolamine at the same dose under long-term (8 days) administration.