Lithospermum, Gromwell, Zi Cao 紫草

Milium Solis, Grommel
Zi Cao (TCM)
Greater and Lesser Gromwell
Dioscorides Materia Medica, Mathias, 1563

Greater and Lesser Lithospermum
Krauterbuch, Lonitzer, 1578

Lithospermum officinale
Oeder, G.C., Flora Danica (1761-1861)

Lithospermum erythrorhizon
(Photo by Doronenko) (Wikimedia)

Botanical name:
Lithospermum spp.
  1. L. officinale
  2. L. erythrorhizon (syn. Lithospermum officinale L. subsp. erythrorhizon) (TCM)

Parts used:
West: Seed; less commonly the leaf or root
TCM: Root

Temperature & Taste:
Cool (TCM) / Mildly Warm (West), dry.

Classification:
B. Clears Heat, Cools the Blood

Uses:
1. Clears Damp, Promotes Urine, Clears Stones: (West, TCM)
-Edema, Dysuria, Strangury
-Gravel and Stones (Seed is regarded as specific)
-also Back Pain and Arthritis
-Seed decocted in Wine is best for these functions
-this is a primary indication in the West, but is also used in TCM

2. Clears Heat, Resists Poison, Promotes Expression of Rashes: (West, TCM)
-Measles, Chicken Pox, Small Pox (TCM, West)
-Quotidian Fever (West)
-also for Hepatitis
-Herb is used for Arthritis in China
-this is a primary indication of the root in TCM, but is also used in the West

3. Moves the Blood, Promotes Menstruation: (West)
-Amenorrhea
-promotes Labor
-has been used as a contraceptive (inhibits gonadotropic hormones)

4. Clears Heat, Calms the Mind:
-more recently, Insomnia, Nervousness (Duke)


DOSE:
Juice: 1–2 oz. were given in Wine.
Root or Seed in Powder: 1–3 grams;
-for Stones, 3 grams of the Powder in wine or emulsion of Cold Seeds.
-to promote Delivery in Labor, 4–6 grams of the Seed powder taken in Woman's Milk, White Wine or Parsley Water. (Salmon)
Root in Decoction: 3–9 grams

COMMENT:
1. TCM uses the root of a Gromwell species, L. erythrorhizon Zi Cao (which is regarded by some as a subspecies of L. officinale). It cools the Blood, clears Heat and Toxin and is primarily used to promote the expression of rashes such as Measles and Chicken Pox. It is also used for urinary dysfunction and Damp-Heat Leukorrhea. The Western and Eastern species are closely related and similar in appearance. The Western species is primarily used for Urinary disorders and the Chinese species for Skin rashes, but they are probably fairly synonymous.
2. Arnebia species are used as Zi Cao in some parts of China. They are also used in Tibetan Medicine (A. euchroma is called 'Bri mog འབྲི་མོག་, A. guttata is called 'Bri rdzud འབྲི་རྫུད་) where they are mainly used for bleeding from the Lungs and increase of 'unhealthy Blood'.

SUBSTITUTE (Alternate species):
Arnebia euchroma and A. guttata are used for Zi Cao in some parts of China.

Main Combinations:
1. To promote Urine, and for Stones, Gromwell seed with the 4 Cold seeds, Parsley seed, Cinnamon and Licorice as in Electuary of Seeds
2. Arthritis and Rheumatism:
i. Gromwell seed with Turbith, Agaric, Ginger, Cassia Wood, Asparagus as in Pills for Arthritis (Nicholas)
3. Back Pain, Arthritis
i. Gromwell seed with Galangal, Zedoary, Celery seed, Asarum as in Decoction for Back Pain and Kidney Stones (Galen)
4. Measles, Skin rashes:'
i. to promote eruption of Skin Rashes, Lithospermum Zi Cao with Burdock seed (Niu Bang Zi), Peppermint (Bo He)
ii. Lithospermum Zi Cao with Forsythia Lian Qiao, Sophora Ku Shen
5. Hepatitis, Lithospermum Zi Cao, Paeonia Mu Dan Pi, Curcuma Yu Jin, Artemisia Yin Chen Hao
6. Gonorrhea, Gromwell seed (3 drams), Amber (1 dram), Ceterach (½ dram); Powder, take 1 dram doses with Juices of Plantain, Purslane, Lettuce (Salmon)
7. Neurodermatitis, cover Lithospermum Zi Cao with Sesame oil. Keep in a warm place for 2 weeks, the strain. Apply twice daily. The same may be dropped in for Prurulent Otitis media.
8. Burns, Lithospermum Zi Cao, Dang Gui (30 grams each), Beeswax (150 grams), Sesame oil (500 mls.). Cook the herbs in the oil until purple-red, strain, add beeswax and form an ointment.


Research
GENERAL / REVIEW
–Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review

ANTI-VIRAL
–Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro

ANTI-INFLAMMATORY
–Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition
–Shikonin Isolated from Lithospermum erythrorhizon Downregulates Proinflammatory Mediators in Lipopolysaccharide-Stimulated BV2 Microglial Cells by Suppressing Crosstalk between Reactive Oxygen Species and NF-κB

IMMUNOSTIMULANT
–Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment

FATTY LIVER DISEASE
–Protective Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract against Hepatic Steatosis in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mice

ULCERATIVE COLITIS
–Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis

ENDOMETRIOSIS
–Novel Drug Targets with Traditional Herbal Medicines for Overcoming Endometriosis

MENOPAUSE
–Prunus mume and Lithospermum erythrorhizon Extracts Synergistically Prevent Visceral Adiposity by Improving Energy Metabolism through Potentiating Hypothalamic Leptin and Insulin Signalling in Ovariectomized Rats

CANCER
–Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine
–In Vitro Screening of Tumoricidal Properties of International Medicinal Herbs: Part II
–Natural Products Targeting the Mitochondria in Cancers
–Shikonin Exerts Antitumor Activity via Proteasome Inhibition and Cell Death Induction in vitro and in vivo
–Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells
–Shikonin Inhibits Cancer Through P21 Upregulation and Apoptosis Induction
–Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells
–Natural products for cancer chemotherapy
BLADDER
–Shikonin suppresses the epithelial-to-mesenchymal transition by downregulating NHE1 in bladder cancer cells
BONE
–The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis
BRAIN
–Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine
–Natural products: a hope for glioblastoma patients
BREAST
–RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment
–Natural Products for the Management and Prevention of Breast Cancer
–Apoptosis induced by β,β-dimethylacrylshikonin is associated with Bcl-2 and NF-κB in human breast carcinoma MCF-7 cells
–Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes
–High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells
–Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells
–Sensitizing the Therapeutic Efficacy of Taxol with Shikonin in Human Breast Cancer Cells
–Phytochemicals: Current strategies for treating breast cancer
COLORECTAL
–Acetylshikonin suppressed growth of colorectal tumour tissue and cells by inhibiting the intracellular kinase, T‐lymphokine‐activated killer cell‐originated protein kinase.
–Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Shikonin in Colon Cancer
–Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer
–Acetylshikonin Induces Apoptosis in Human Colorectal Cancer HCT-15 and LoVo Cells via Nuclear Translocation of FOXO3 and ROS Level Elevation
–Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells
–Effect of β,β-Dimethylacrylshikonin on Inhibition of Human Colorectal Cancer Cell Growth in Vitro and in Vivo
–Shikonin regulates invasion and autophagy of cultured colon cancer cells by inhibiting yes-associated protein
–Traditional Chinese Medicine and Colorectal Cancer: Implications for Drug Discovery
–Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis
ESOPHAGEAL
–Shikonin Promotes Apoptosis and Attenuates Migration and Invasion of Human Esophageal Cancer Cells by Inhibiting Tumor Necrosis Factor Receptor-Associated Protein 1 Expression and AKT/mTOR Signaling Pathway
–Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo
GASTRIC
–β,β-Dimethylacrylshikonin Induces Mitochondria Dependent Apoptosis through ERK Pathway in Human Gastric Cancer SGC-7901 Cells
–Shikonin induces apoptosis in the human gastric cancer cells HGC-27 through mitochondria-mediated pathway
–Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species
LIVER
–A new meroterpenoid functions as an anti-tumor agent in hepatoma cells by downregulating mTOR activation and inhibiting EMT
–Experimental Study of Hepatocellular Carcinoma Treatment by Shikonin Through Regulating PKM2
–Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma
–Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside
LUNG
–Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells
–Anti-tumor activity of Shikonin against afatinib resistant non-small cell lung cancer via negative regulation of PI3K/Akt signaling pathway
–Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 Expression
–Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment via the IL-6/STAT3 signaling pathway
–Senescence Inducer Shikonin ROS-Dependently Suppressed Lung Cancer Progression
–Quinonoids: Therapeutic Potential for Lung Cancer Treatment
–Shikonin Inhibits Non-Small-Cell Lung Cancer H1299 Cell Growth through Survivin Signaling Pathway
MELANOMA
–Shikonin inhibits proliferation of melanoma cells by MAPK pathway-mediated induction of apoptosis
–Applicability of Plant Extracts in Preclinical Studies of Melanoma: A Systematic Review
MYELOMA
–Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells
OVARIAN
–Shikonin induces apoptosis and inhibits migration of ovarian carcinoma cells by inhibiting the phosphorylation of Src and FAK
–Combination of shikonin with paclitaxel overcomes multidrug resistance in human ovarian carcinoma cells in a P-gp-independent manner through enhanced ROS generation
–Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells
PANCREATIC
–Shikonin induces apoptosis and necroptosis in pancreatic cancer via regulating the expression of RIP1/RIP3 and synergizes the activity of gemcitabine
–Regulation and function of autophagy in pancreatic cancer
PROSTATE
–Prostate cancer and the unfolded protein response
–Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway
–Shikonin inhibits the growth of human prostate cancer cells via modulation of the androgen receptor
–Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis
SKIN
–Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation
STOMACH
–Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells
THYROID
–Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

DERMATITIS
–Effect of Lithospermi Radix on Contact Dermatitis Induced by Dinitrofluorobenzene in Mice

PSORIASIS
–Shikonin inhibits CEBPD downregulation in IL-17-treated HaCaT cells and in an imiquimod-induced psoriasis model

COSMETIC
–Improved cosmetic activity by optimizing the Lithospermum erythrorhizon extraction process
–Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity

WOUND HEALING
–Wound Healing and the Use of Medicinal Plants