Anti-cancer activities of ginsenosides

“Cancer opens many doors. One of the most important is your heart.”

Greg Anderson

Ginsenosides are the main bioactive dammarane triterpenoids derived from the rhizomes of many plants, including

• Panax notoginseng (Burk.) F. H. Chen, commonly referred to in English as Chinese ginseng or notoginseng,
• Panax ginseng, also known as Korean ginseng and
• Cinnamomum cassia Presl., called also Chinese cassia or Chinese cinnamon,

and they have various biological effects including anti-oxidative, anti-inflammatory and anti-cancer activities (Source: "Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine").

So far, many pharmacological properties of ginsenosides have been verified by modern science, and include among other things immune response boosting, anti-inflammatory, hepatoprotective, anti-obesity, anti-microbial, cognition enhancement and antioxidant effects. Accordingly, the root of ginseng is currently used for treating cardiovascular diseases, autoimmune diseases, cancer, Alzheimer's disease, stress-induced diseases, ocular disease and diabetes.

Regarding cancer, ginsenosides (the saponin components in ginseng) mainly exert anti-cancer effects (Source) in

• colorectal,
• breast (Source Via Vocal: "Fighting breast cancer with natural compounds backed by science"),
• brain,
• gastric,
• liver and
• lung cancers,

through inhibition of cell proliferation, cell migration and angiogenesis (Source Via Vocal: "Fighting angiogenesis with natural compounds backed by science"), and also through reversing drug resistance. The primary bioactive compounds among ginsenosides for cancer prevention are ginsenoside Rg3, ginsenoside Rh2 and the compound K.

For example, Rg3 inhibits cell viability and induces cell apoptosis in human ovarian cancer, hepatocellular carcinoma, breast cancer, non-small-cell lung carcinoma and Lewis lung carcinoma cells. Rg3 can also modulate the tumour environment through inhibition of angiogenesis and enhancement of anti-tumour immune responses.

Regarding brain cancer, Rg3 can improve the efficiency of temozolomide, sold under the brand name Temodar among others is a medication used to treat some brain tumours such as glioblastoma multiforme or anaplastic astrocytoma, in temozolomide-resistant glioblastoma. Additionally, Rg3 can ameliorate senescence (a process by which a cell ages and permanently stops dividing but does not die) which is one of the side effects of chemotherapy treatment in glioblastoma (senescence is activated in response to chemotherapy to prevent the propagation of cancer cells), and can have neuroprotective properties against brain-related diseases.

Moreover, Rh2 exhibits anti-tumour activity in human non-small-cell lung carcinoma cells and xenograft mice, through the induction of apoptosis. It also suppresses cell proliferation and migration, and induces cell cycle arrest in human hepatocellular carcinoma cells and inhibits tumour growth in hepatocellular carcinoma xenograft mice. Rh2 can also up-regulate the expression of miR-491 (inhibits metastasis and epithelial to mesenchymal transition in hepatocellular carcinoma and esophageal cancer) and miR-146a-5p, which both play important roles in the development and progress of hepatocellular carcinoma. Moreover, Rh2 combined with regorafenib (an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase) suppressed hepatocellular carcinoma cell growth by up-regulating genes of the apoptosis-inhibiting gene family.

The compound K, an intestinal bacterial metabolite of ginsenosides, also induces cell cycle arrest and apoptosis in human colorectal cancer cells, and suppresses tumour growth in xenograft mice. It also efficiently inhibits cell proliferation and induces apoptosis through mitochondrial-related pathways in human hepatocellular carcinoma cells.

Moreover, the compound K can induce autophagy-mediated apoptosis and can suppress cell viability by down-regulating Hypoxia-inducible factor 1 (HIF-1α) mediated glucose metabolism in human non-small-cell lung carcinoma. Emerging evidence suggests that HIF-1α plays an important role in the pathogenesis of cancer, since hypoxia is a condition always present in tumour environment owing to the fast growth of tumour cells not supported by adequate blood supply.

Immunity and ginsenosides

For the promotion of immunity, Rg3 can enhance 1) lymphocyte proliferation (a type of white blood cell that is part of the immune system, with two main types of lymphocytes: B cells and T cells) and 2) T helper type 1 cell ( 1)-related cytokine secretion (TH2 cells are excellent helpers for B-cell antibody secretion) in hepatacellular carcinoma bearing mice, and can inhibit tumour growth partly through the induction of cellular immunity.

In addition, Rh2 can enhance anti-tumour immunity in melanoma mice by promoting T cell infiltration in the tumour and cytotoxicity in spleen lymphocytes.

Combination of ginsenosides with other chemo-therapeutic agents

The combination of ginsenosides with other chemo-therapeutic agents provides significant advantages for cancer treatment. For example, the combined treatment Rg3 and temozolomide (sold under the brand name Temodar among others, is a medication used to treat some brain tumours such as glioblastoma multiforme or anaplastic astrocytoma) displays additive anti-angiogenic effects in B6 glioblastoma rats. And when Rg3 is combined with paclitaxel (sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer) it enhances cytotoxicity and apoptosis through NF-κB inhibition in human triple-negative breast cancer cells.

Finally, a clinical trial showed that Rg3 in combination with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced non-small-cell lung carcinoma, increased the progression-free survival, overall survival and objective response rate compared to EGFR-TKI alone. And in another study, combined Rg3 and transcatheter arterial chemo-embolisation (TACE), namely local delivery of chemotherapy with a procedure called immobilisation to treat cancer, showed that the combined therapy ameliorated TACE-induced adverse effects and prolonged the overall survival compared to the use of TACE alone.

P.S.

Patented method (Google patents CN1083663A) for preparation of "red ginseng tea"

Percentage (wt%)

Red ginseng 10～15% (also known as Asian ginseng or Panax ginseng and shouldn’t be confused with Siberian ginseng or American ginseng)

Rhodiola root 20～25%

Black tea 40～45%

Brown sugar 10～25%

And just enjoy 🌝

“The tea ceremony is like any other art where years of study are necessary to do it with grace and a depth of understanding and skill. The masters say that it takes ten years of dedicated study to do it right.”

A.L. Sadler