Developing a Rational, Optimized Product of Centella asiatica for Examination in Clinical Trials: Real World Challenges

Botanical products are frequently sold as dietary supplements and their use by the public is increasing in popularity. However, scientific evaluation of their medicinal benefits presents unique challenges due to their chemical complexity, inherent variability, and the involvement of multiple active components and biological targets. Translation away from preclinical models, and developing an optimized, reproducible botanical product for use in clinical trials, presents particular challenges for phytotherapeutic agents compared to single chemical entities. Common deficiencies noted in clinical trials of botanical products include limited characterization of the product tested, inadequate placebo control, and lack of rationale for the type of product tested, dose used, outcome measures or even the study population. Our group has focused on the botanical Centella asiatica due to its reputation for enhancing cognition in Eastern traditional medicine systems. Our preclinical studies on a Centella asiatica water extract (CAW) and its bioactive components strongly support its potential as a phytotherapeutic agent for cognitive decline in aging and Alzheimer's disease through influences on antioxidant response, mitochondrial activity, and synaptic density. Here we describe our robust, scientific approach toward developing a rational phytotherapeutic product based on Centella asiatica for human investigation, addressing multiple factors to optimize its valid clinical evaluation. Specific aspects covered include approaches to identifying an optimal dose range for clinical assessment, design and composition of a dosage form and matching placebo, sourcing appropriate botanical raw material for product manufacture (including the evaluation of active compounds and contaminants), and up-scaling of laboratory extraction methods to available current Good Manufacturing Practice (cGMP) certified industrial facilities. We also address the process of obtaining regulatory approvals to proceed with clinical trials. Our study highlights the complexity of translational research on botanicals and the importance of identifying active compounds and developing sound analytical and bioanalytical methods for their determination in botanical materials and biological samples. Recent Phase I pharmacokinetic studies of our Centella asiatica product in humans (NCT03929250, NCT03937908) have highlighted additional challenges associated with designing botanical bioavailability studies, including specific dietary considerations that need to be considered.

Honeybee and Plant Products as Natural Antimicrobials in Enhancement of Poultry Health and Production

The quality and safety attributes of poultry products have attracted increasing widespread attention and interest from scholarly groups and the general population. As natural and safe alternatives to synthetic and artificial chemical drugs (e.g., antibiotics), botanical products are recently being used in poultry farms more than 60% of the time for producing organic products. Medicinal plants, and honeybee products, are natural substances, and they were added to poultry diets in a small amount (between 1% and 3%) as a source of nutrition and to provide health benefits for poultry. In addition, they have several biological functions in the poultry body and may help to enhance their welfare. These supplements can increase the bodyweight of broilers and the egg production of laying hens by approximately 7% and 10% and enhance meat and egg quality by more than 25%. Moreover, they can improve rooster semen quality by an average of 20%. Previous research on the main biological activities performed by biotics has shown that most research only concentrated on the notion of using botanical products as growth promoters, anti-inflammatory, and antibacterial agents. In the current review, the critical effects and functions of bee products and botanicals are explored as natural and safe alternative feed additives in poultry production, such as antioxidants, sexual-stimulants, immuno-stimulants, and for producing healthy products.

A review of nano and micro-encapsulated phytochemical compounds for disease management in agriculture

Plant extracts (PEs) and essential oils (EOs) contain phytochemical compounds (PCs). Nevertheless, PCs can be degraded when applied on field. The use of nano-encapsulates (NEs) and micro-encapsulates (MEs) arise as an alternative to the application of botanical products. However, NEs and MEs with PCs in plant disease control have not been explored enough. This review discusses the use of PCs for plant disease control and the benefits obtained from formulations with NEs and MEs; furthermore, it discusses methods to produce NEs and MEs.

Deterrent Effects of Essential Oils on Spotted-Wing Drosophila (Drosophila suzukii): Implications for Organic Management in Berry Crops

Due to concerns about frequent applications of spinosad and other broad spectrum insecticides for managing spotted-wing drosophila (Drosophila suzukii Matsumura, SWD), we investigated the use of essential oils as an alternative to current insecticides. Essential oils from a number of plant species have been studied for their attraction and deterrence of SWD. However, these botanical products have not been thoroughly tested in the field. We conducted laboratory and field studies to determine the efficacy of botanical products, including lavender (Lavandula angustifolia Mill.) oil, catnip (Nepeta cataria L.) oil, KeyPlex Ecotrol® PLUS, and KeyPlex Sporan® EC2 on preventing SWD infestation in raspberry (Rubus idaeus L.) and blueberry (Vacciniumcorymbosum L.) crops. In a two-choice laboratory bioassay, lavender oil, Ecotrol, and Sporan treatments deterred SWD from a yeast-cornmeal-sugar based fly diet. In the field trials, raspberry fruit treated with Ecotrol had lower SWD infestation (6%), compared to the control (17%), and was comparable to spinosad (6%). No differences were seen in blueberry infestation. The combination of essential oils in Ecotrol may work to decrease SWD fruit infestation under certain conditions in the field, however more research is needed on the longevity of these products.

Botanical Products in the Treatment and Control of Schistosomiasis: Recent Studies and Distribution of Active Plant Resources According to Affected Regions

Schistosomiasis, a parasitic disease caused by trematodes of the genus Schistosoma, is the second most prevalent parasitic disease in the world. It affects around 200 million people. Clinical treatment, prophylaxis, and prevention are performed in countries susceptible to schistosomiasis. In the pharmacological treatment for an acute form of schistosomiasis, the use of antiparasitics, mainly praziquantel, is more common. As an alternative way, prevention methods such as reducing the population of intermediate hosts (mollusks) with molluscicides are important in the control of this disease by interrupting the biological cycle of this etiological parasite. Despite the importance of pharmacological agents and molluscicides, they have side effects and environmental toxicity. In addition, they can lead to the development of resistance enhancing of parasites, and lead to the search for new and effective drugs, including resources of vegetal origin, which in turn, are abundant in the affected countries. Thus, the purpose of this review is to summarize recent studies on botanical products with potential for the control of schistosomiasis, including anti-Schistosoma and molluscicide activities. In addition, species and plant derivatives according to their origin or geographical importance indicating a possible utility of local resources for countries most affected by the disease are presented.