ImmunAG: Phyto-therapy and human civilization

by | Feb 13, 2019

Written by Kristina Etter

Kristina is a digital content creator and designer. She has a talent for creating engaging and informative content that resonates with our professional audience. Kristina’s passion for the cannabis industry stems from her belief that it has the potential to revolutionize the world in many ways, and has a personal testimony of cannabis success.

Humans have used plants as medicine as far back as the Middle Paleolithic age 60,000 years ago1. According to the World Health Organization (WHO), almost 65% of the world’s population have incorporated plants into their primary mode of health care2. Traditional Indian Medicine and Traditional Chinese Medicines have been part of the two largest cultures for thousands of years.

CNS & Immune system connection

It is critical for the central nervous system to be completely in sync with the immune system. The mechanism for this obviously important connection was unknown until recently. The connection was discovered five years ago and the new modulators were tagged as “unconventional neurotransmitters”. These new unconventional neurotransmitters don’t follow the rules of the traditional neurotransmitters. The two classes of unconventional transmitters (so far) are “endocannabinoids” and “gasotransmitters” (soluble gases such as nitric oxide and carbon monoxide). These molecules are unconventional in that-

  1. They are not stored in synaptic vesicles.
  2. They carry messages from the postsynaptic neuron to the presynaptic neuron.
  3. Rather than interacting with receptors on the plasma membrane of their target cells, they can cross the cell membrane and act directly on molecules inside the cell.

Other unconventional messengers will be discovered as we learn more and more about how neurons work. As new chemical messengers are discovered, we will have to further change our idea of what it means to be a neurotransmitter.

CB2 mediates CNS & immune system

The newly discovered endocannabinoid system has a receptor called CB2. The density of CB2 in the human body gives away its importance-

Immune system

CB2 receptors are found in the peripheral tissues of the immune system5. They are found throughout tissues of the spleen, tonsils, and thymus gland5. They are localized on immune cells such as monocytes, macrophages, B-cells, and T-cells5,6,7. The greatest density of CB2 in the human body is in the spleen.

Brain

CB2 receptors are found primarily on microglia8. CB2 receptors have functional relevance in the CNS and in particular in neural signal transmission9.

Gastrointestinal system

CB2 receptors are found throughout the gastrointestinal system, where they modulate intestinal inflammation10. The CB2 receptor is critical for inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis10,11. Dysfunction of this system plays a role in irritable bowel syndrome12.

Peripheral nervous system

CB2-specific receptors are also involved in analgesic effects in the peripheral nervous system. They possibly influence mast cells, known to facilitate the inflammatory response13.

In 2011, Professor Mechoulam documented that change in CB2 receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer4. The trend linking CB2 to diseases has continued. This suggests that normalizing CB2 receptor activity (bringing it back to homeostasis) holds unique therapeutic potential.

The hunt for CB2 modulators

The importance of CB2 in human health, and in cancer immunotherapy is being rapidly recognized. Numerous companies are racing to develop synthetic agonists, antagonists and inverse agonists for CB2.

Our approach has been to find natural modulators for CB2 from plants. Humans and cancer cells are cumbersome to use in scientific studies. So we developed a mimotope of the CB2 receptor (being patented) and used it to rapidly test the various modulators extracted from plants. Some of the plants that modulate CB2 well are-

  1. Oxeye plants – Heliopsis helianthoides18
  2. Coneflower – Echinacea purpurea19,20
  3. Electric Daisy – Acmella oleracea21,22
  4. South African Daisy- Helichrysum umbraculigerum23
  5. Liverwort – Radula marginata24
  6. Chocolate – Theobroma cacao25
  7. Black pepper – Piper nigrum26
  8. Chinese Rhododendrum – Rhododendron anthopogonoides27
  9. Flax – Linum usitatissimum28
  10. Beer Hops – Humulus Lupulus L29

Humulus kriya and Humulus Ooty

Humulus lupulus has a long history as a medicinal remedy32. In India, the Ayurvedic Pharmacopoeia recommends Humulus lupulus to treat restlessness associated with nervous tension, headache, and indigestion33.

In 1799, Tipu Sultan ceded the Nilgiris, by the treaty of Srirangapatnam to the British East India Company. In 1819, John Sullivan built his bungalow in Dimbhatti, Ooty. He was enthralled by the place35. Sullivan planted may trees and plants in his estate. One of the plants was considered very medicinal and was particularly effective against tuberculosis36. In 1936 Hu identified the plant as Humulus yunnanensis that was originally localized in Kashmir and Himachal Pradesh near the Himalayan mountains34. Presumably, Sullivan had it planted in Ooty.

Ooty was the summer capital of the Madras Presidency and was the home of the Madras Regiment of the Indian Army37. After the British left India Ooty became a popular tourist destination. The plants that Sullivan planted grew feral.

In 1998, KK Shanmuga Dasan, a scientist at Central Drug Research Institute, India, studied the medicinal properties of samples of Humulus obtained from Ooty. In 2000, Dr. Avi Cohen and Dr. Bomi Joseph collected 23 samples of female Humulus and 7 samples of male Humulus from Ooty. Dr. Avi Cohen is a Member of the Research Committee of the Israeli Scientific Cooperative on Phytotherapy, and advisor to the International Foundation for Science in Tel Aviv, Israel. Dr. Bomi Joseph is an oncologist and a founder and director of ImmunAg LP. He is a leading authority on food and drug safety, drug intolerance and food-related diseases. He currently advises leading food and pharmaceutical companies and the World Health Organization in the areas of food and drug safety, additives, foodborne diseases, and genetically modified foods.

All the samples collected by Dr. Cohen and Dr. Joseph had imperfect flowers, with separate staminate “male” and pistillate “female” flowers occurring on separate plants. Male and female plants are easily distinguished by their differing flowers. The male flowers are long racemes, 7.5–12.5 cm long, while the female inflorescences are cone-like catkins (called strobiles), 2.5–5 cm long, made up of overlapping membranaceous bracts. The external bracts are flattened and symmetrical. The internal bracts are longer and generally enfolding at the base a small fruit (achene). A resinous substance, named lupulin, is secreted by yellow glandular trichomes found at the base of cone bracts and can be separated by shaking the strobiles. Lupulin-like glands are also present on the underside of the leaves. Female strobiles were collected in August–September when they are ripe and their color changes from pale greenish-yellow to yellow-brown. Only female individuals are planted in isolated greenhouses in order to maintain a genetically consistent product. Males were used for breeding and to develop new varieties through controlled hybridization.

Various hybrids were bred were for increased production of the terpenoid compounds β-caryophyllene, humulene (sesquiterpene), myrcene (monoterpene). A hybrid which produced significant terpenoids was a recessive plant that produced reduced amounts of bitter acids. This hybrid was named Humulus Ooty and its GC-Mass Spec. pattern can be seen in Figure 1.

Figure 1

Another recessive hybrid which produced very little bitter acids also produced very little terpenoid compounds was discovered by Dr. Joseph in 2014 in the Himalayan tracts of the Indo-China border. This hybrid produced larger molecular weight compounds which were identified to be pentyl benzenediols such as Cannabigerol, Cannabichromene, and Cannabidiol. As the medicinal properties of these compounds started being discovered by Professor Mechoulem4, Dr. Joseph started breeding this hybrid in earnest. He named this variant Humulus kriya (Kriya in Sanskrit means “life”) and its GC-MS profile is attached as Figure 2.

ImmunAg

The raw ImmunAG is the extract of Humulus kriya and it is a rich profile of β-Caryophyllene, Farnesene, α-Humulene, Humulone, Lulpulone, Xanthohumol, 6-Prenylnaringenin, Cannabichromene, Δ-2 Cannabidiol, Cannabigerol. Every one of these ingredients modulates the CB-2 receptor in some manner. The assay and analysis of native ImmunAG can be seen in Figure 3.

All the components of ImmunAg are approved for use by the Food Safety and Standards Authority of India (License # 10018025000320), the European Food Safety Authority, and the German Bundesanstalt für Landwirtschaft und Ernährung (Food Safety and Protection Agency).

All the components of ImmunAg are considered “safe” by the FDA because they are on the GRAS list (“The history of consumption of the substance for food use by a significant number of consumers (or animals in the case of animal food) prior to January 1, 1958, if a conclusion of GRAS status is based on common use of the substance in food prior to 1958 (Part 5)”).

ImmunAg has had considerable success as a dietary supplement and as an adjuvant treatment for various diseases.

For more information about ImmunAG visit their website at www.immunag.org

|References|

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