Over the past several years, we have seen a huge increase in clients who are turning to us to help test the efficacy of their natural compounds, plants, and formulations. Our simple animal models — namely, the Nobel Prize — winning microscoping roundworm C. elegans and the zebrafish Danio rerio — help nutraceutical and pharmaceutical companies alike bridge the gap between cell culture and human clinical trials, without the time and expense required for mouse studies. Our model animals may be small and simple — but due to the common genetics underlying so much of the tree of life, the scientific answers we can provide using these animals are really predictive of how big animals like humans will respond to treatment with the same compounds. Over time, we have developed distinct Platforms that help companies answer questions like: Does my formulation prevent mitochondria from degrading with age? How does my ingredient compare to well known antioxidants like Vitamin C? What markers of inflammation might decrease when I go into a clinical trial? Will my compound lead to longer, healthier lives?
Recently, we have decided to partner with Chenland Nutritionals, Inc., utilizing our suite of in vivo platforms to test the efficacy of their longevity product, JadeAging®. Based on Traditional Chinese Medicine, the formula’s active ingredients are naturally derived: Rehmanniae Radix, Poriae, and Ginseng Radix. In this experiment we will focus on lifespan, healthspan, and transcriptional changes related to aging, and we will document all of it — this article will be the first in a blog-along series where we will walk through our experimental process. So let’s get started!
Introducing Chenland Nutritionals, Inc.
Chenland Nutritionals, Inc. is a manufacturer, supplier, and marketer of natural ingredients and clinically proven formulations. Chenland Nutritionals, Inc. has developed formulations that target joint health, bone health, immunity, mood, and menopausal health. Chenland Nutritionals, Inc. is guided by the principles of Traditional Chinese Medicine (TCM). For over 2,000 years TCM has utilized herbs and plant derivatives to improve health. Chenland Nutritionals, Inc. utilizes these long-established herbs and new scientific technology to develop more efficient formulations.
The History of Traditional Chinese Medicine (TCM)
Traditional Chinese Medicine consists of acupuncture, tai chi, and herbal products. Chinese herbal medicine has a long historical tradition, and was protected and supported by Chinese emperors throughout the years, meaning that clearly written records exist for nearly 2,000 years of patients (Cleveland Clinic, 2021). Chinese herbal medicine differs from Western herbalism in that Chinese herbal medicine focuses on the patient as a whole rather than treating one symptom or disease (NIH, 2019). Furthermore, Chinese herbal medicine utilizes herbal combinations rather than prescribing a single-herb supplement as is common in Western herbalism (Winchester Hospital, n.d.). Chinese herbal medicine has many proposed uses including, but not limited to: helping patients who complain of allergies, autoimmune disorders, cancer treatment side effects, diarrhea and constipation, digestion issues, infertility, irritable bowel syndrome, menopause, menstrual/endometriosis pain, and persistent fatigue (Cleveland Clinic, 2021). Nowadays, Chinese Herbal Medicine is used alongside pharmaceutical treatment, and there is increasing interest from the Western medical community to see whether TCM can help inform or provide better treatment options. In fact, the NIH has specifically called out the need for more research into natural products — recently declaring that research into “complex interactions involving nutritional interventions'' is one of the National Center for Complementary and Integrative Health (NCCIH)’s top priorities, according to their 2021-2025 Strategic Plan (NIH, 2021).
The longevity product: JadeAging®
The longevity formulation that we will be testing is composed of three main active ingredients: Rehmanniae Radix, Poriae, and Ginseng Radix [Table 1].
|Rehmanniae Radix||Plant root||Anemia, kidney disease, obesity, and diabetes (Kim et al., 2017).|
|Poriae (Wolfiporia cocos)||Mushroom||Memory, anxiety, and fatigue (WebMD, 2020).|
|Ginseng Radix||Herb||Memory, depression, erectile dysfunction, flu, and fatigue (Semeco, 2018).|
Table 1. Ingredients in Chenland’s longevity formula, JadeAging®
Designing the Experiment
Stacy, our Scientist I, did research into these naturally derived ingredients, their effect on health, and what genetic pathways may be involved in causing these effects.
- Inhibits apoptosis, degranulation, and inflammation of cells
- Inhibited production of NFkB and ROS
- Inhibit angiogenesis and neovascularization
- Affects blood sugar
Affects the immune system through the pathways (Chae & Yang, 2007):
- Inhibits NFkB signaling
- Reduces angiogenesis
- Increases insulin sensitivity and decreases blood glucose
- Has anti-inflammatory properties through inhibition of PLA2
- Cytotoxic to cancer cells and inhibits their proliferation
Affects the immune system through the pathways (Zhang et al., 2021):
- Increases ghrelin and leptin
Inhibits production of proinflammatory signals (Liu et al, 2020).
Our goal for this experiment is to use our suite of in vivo Platforms to give insight into the longevity and health-promoting effects JadeAging®’s active ingredients: Rehmanniae Radix, Poriae, and Ginseng Radix, and uncover how these ingredients work at the mechanistic and genetic level. We will be using the following platforms to achieve these objectives.
- Vitality Platform: We perform lifetime monitoring on a large population of animals to determine whether compounds and formulations affect lifespan and healthspan.
- Genetic Signature Platform: We determine how a compound or formulation affects gene expression using RNAseq and transcriptomics technology. We then distill this information into specific guidance on what to look for in clinical studies and substantiation of structure/function claims.
- Antioxidant Capacity Platform: We uncover whether a compound or formulation has antioxidant properties using a standardized reactive oxygen species exposure assay.
- Mitochondrial Function Platform: We investigate the impact of a compound or formulation on mitochondrial function across the lifespan utilizing fluorescent imaging of mitochondrial structures.
These platforms will enable our partners at Chenland to quickly determine the next steps for their product: be that attracting new investment, or deliver new validation of marketing claims to increase sales. For instance, our Vitality Platform can deliver information on the lifespan and healthspan effects of a compound on hundreds of animals within only 4 months.
The Vitality Platform works by video recording the movement and morphology of the C. elegans animal model. Known as the “Gold-standard” for longevity studies, these nematodes will provide a rich dataset of biometrics that span the animal’s entire lifespan [Figure 1].
Figure 1. The vitality platform detected a significant positive increase in lifespan at all concentrations of Compound A, especially at the highest concentration. Compound A yielded as big of a lifespan extension as the positive control treated group.
Our Vitality Platform also measures the transcriptional changes related to aging that the animals experience after being treated with the compounds of interest. This will provide Mechanism of Action information which reveals pathway activity related to the compounds [Figure 2].
Figure 2. Summary of affected gene pathways. Gene pathways related to healthy-aging were largely upregulated by treatment with Compound A. Genes are put into pathways using gene ontological analysis.
As previously mentioned, we will be blogging each milestone of our experimental process. First up is our dosage study, so check back to read more about Phase 1: dose optimization.
Winchester Hospital (n.d.). Traditional Chinese Herbal Medicine. Beth Israrl Lahey Health, Winchester Hospital, https://www.winchesterhospital.org/health-library/article?id=37410
Cleveland Clinic (2021). What You Should Know About Chinese Herbs, Cleveland Clinic, Healthessentials, https://health.clevelandclinic.org/what-you-should-know-about-chinese-herbs/
NIH (2019). Traditional Chinese Medicine: What You Need To Know. NIH, National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/traditional-chinese-medicine-what-you-need-to-know
NIH (2021). Natural Products Research—Information for Researchers. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/grants/natural-products-research-information-for-researchers
Kim, S. H., Yook, T. H., & Kim, J. U. (2017). Rehmanniae Radix, an Effective Treatment for Patients with Various Inflammatory and Metabolic Diseases: Results from a Review of Korean Publications. Journal of pharmacopuncture, 20(2), 81–88. https://doi.org/10.3831/KPI.2017.20.010
WedMD (2020). Poria Mushroom - Uses, Side Effects, and More. WebMD. https://www.webmd.com/vitamins/ai/ingredientmono-246/poria-mushroom
Semeco, A. (2018). 7 Proven Health Benefits of Ginseng. Healthline. https://www.healthline.com/nutrition/ginseng-benefits#TOC_TITLE_HDR_1
Chae BS, Yang JH. (2007) Regulatory effect of fresh rehman-niae radix extract on the in vitro production of proin-ammatory cytokines in pristane-induced lupus mice. Nat Prod Sci. ;13(4):322-7.
Zhang, L., Yin, M., Feng, X., Ibrahim, S. A., Liu, Y., & Huang, W. (2021). Anti-Inflammatory Activity of Four Triterpenoids Isolated from Poriae Cutis. Foods (Basel, Switzerland), 10(12), 3155. https://doi.org/10.3390/foods10123155
Liu, H., Lu, X., Hu, Y., & Fan, X. (2020). Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy. Pharmacological research, 161, 105263. https://doi.org/10.1016/j.phrs.2020.105263