Scutellaria baicalensis &

Baicalin

• Recent trends in medicinal plants research show that while ethnobotanical surveys continue, there is an appreciable increase in research activity in the area of bioactivity of natural products. As many as 84% of pediatric oncology patients, 50% of breast cancer patients and 37% of prostate cancer patients use complementary and alternative medicine (CAM), including predominantly herbal approaches

Scutellaria

Scutellaria is a perennial, herbaceous genus in the Lamiaceae family with 350 - 400 species This genus is well represented by about 90 species in the North America.

Scientific classification• Kingdom: Plantae• Order: Lamiales• Family: Lamiaceae• Subfamily: Scutellarioideae• Genus: Scutellaria

Species include :- • Scutellaria baicalensis Georgi – Baikal skullcap,

Chinese skullcap• Scutellaria californica A.Gray – California

skullcap• Scutellaria lateriflora L. – blue skullcap,

Virginian skullcap• Scutellaria montana Chapm. – mountain

skullcap, large-flowered skullcap• Scutellaria ovata Hill – heart-leaved skullcap• Scutellaria racemosa – South American skullcap• Scutellaria wrightii – Wright's skullcap• Scutellaria texana – Texas skullcap

• The scullcap (skullcap) is a North American perennial plant that grows in wet places in Canada and the northern and eastern U.S.

• Successful micropropagation of many Scutellaria species have been reported It has been estimated that the annual consumption of scullcap increased by 23% between 2000 and 2001.

• The dollar value of the 2001 scullcap harvest was between $185,000 and $195,000, that was 3.5 times higher than that of 1997 As the demand for medicinal herb is increasing, there is renewed interest in this genus to propagate clean plants and biomass in large amount

Scutellaria baicalensis

S. baicalensis is the most extensively studied species of Skullcap

Scutellaria baicalensis, Chinese skullcap has been widely used as a medicinal plant in China for thousands of years (2000) , as a traditional medicine known as (Huang-Qin) ,where the preparation from its roots

• The most authoritative book on traditional Chinese medicine, Bencao Gangmu , which was first published in 1593, reported that Scutellaria baicalensis had been used in the treatment : -

diarrhea,hypertension, hemorrhaging, insomnia, inflammation and respiratory infections

• Flavones such as baicalin, wogonoside and their aglycones baicalein, wogonin are the major bioactive compounds extracted from the root of

S. baicalensis.

• These flavones have been reported to have various pharmacological functions, including

• anti-cancer, • hepatoprotection, • antibacterial and antiviral,• antioxidant, • and neuroprotective effects

• Huang-Qin was first recorded in Shennong Bencaojing (The Classic of Herbal Medicine), written between about 200 and 250 AD, for treatment of bitter, cold, lung and liver problems

• Its author, Li Shizhen, reported successful self-administration to treat a severe lung infection when he was 20 years old

• As in traditional Chinese medicine, the roots of S. amoena and S. likiangensis have been used commonly as alternatives to S. baicalensis

Pharmacology of Huang-Qin

Antitumor effects:

Many studies have shown that S. baicalensis extract is cytotoxic to a broad range of cancer cells from humans, including : • brain tumor cells• prostate cancer cells• HNSCC (head and neck squamous cell

carcinoma) cell lines

• Aqueous extracts of S. baicalensis roots induced apoptosis and therefore suppressed growth of lymphoma and myeloma cell line

• Similarly, S. baicalensis extracts were selectively toxic to several human lung cancer cell lines, but not to normal human lung fibroblasts

• Wogonoside has anticancer effects on acute myeloid leukemia (AML) cell lines

Hepatoprotection

• Scutellaria baicalensis is the main component in the herbal remedy used for liver problems such as hepatitis, hepatic fibrosis and carcinoma .

• Yang-GanWan (YGW) is another prescription containing baicalin, which has long been known for its protective effects on the liver

• Several studies have suggested that S. baicalensis can effectively inhibit fibrosis and lipid peroxidation in rat liver

• Consumption of the roots and shoots of S. baicalensis inhibits mutagenisis caused by the aflatoxin-B1 mycotoxin in rat liver cells

Antibacterial and antiviral activities

• Amongst 46 herb and spice extracts, S. baicalensis extracts have shown substantial antibacterial effects against

• Bacillus cereus,• Escherichia coli, • Listeria monocytogenes,• Salmonella anatum • Staphylococcus aureus

• Aqueous extracts of S. baicalensis roots have antimycotic properties against

• Aspergillus fumigatus,• Candida albicans, • Geotrichum candidum • Rhodotorula rubra

• Extracts of S. baicalensis can also enhance the antimicrobial activity of several antibiotics such as

• ciprofloxacin, • ceftriaxone, • Gentamicin• penicillin

• indicating an antiviral function of Scutellaria extracts

• Scutellaria root extracts can inhibit the replication of HCV-RNA .

• Baicalin has very good anti-HIV-1 activity as a nonnucleoside reverse transcriptase inhibitor

• Early in 1989, Ono et al. reported baicalein could effectively inhibit reverse transcriptase activity of human immunodeficiency virus (HIV); 2 μg/mL baicalein inhibiting 90 % of the activity of HIV reverse transcriptases

• These effects of baicalein and baicalin on HIV have attracted considerable attention

Biotechnology to enhance S. baicalensis synthesis

• Understanding the regulation of production of bioactive flavones (baicalein, baibalin, wogonin and wogonoside) and their biosynthesis in S. baicalensis, and developing strategies to enhance their production are important objectives. However, like other members of the mint family, stable genetic transformation and regeneration of this plant are very difficul

• Agrobacterium rhizogenes mediated production of hairy roots of S. baicalensis

• A. rhizogenes strain-dependant manner. Among the four strains (A4GUS, R1000 LBA 9402 and ATCC11325) tested by Tiwari et al.(2008), the A4 stain produced the most hairy roots, with an efficiency of 42.6 %

Flavonoid metabolism

• Scutellaria baicalensis Georgi produces various natural products including amino acids, essential oils, flavonoids, phenylethanoids, and sterols. More than 30 types of flavones can be found in its roots including baicalin, baicalein, chrysin, oroxylin A, oroxylin A 7-O-glucuronide, wogonin and wogonoside.

• Flavones are synthesized by the flavonoid pathway, which is part of phenylpropanoid metabolism

• Naringenin is a central intermediate in normal flavone biosynthesis exemplified by the production of the flavones, scutellarin and scutellarein, derived from naringenin in the aerial parts (leaves and flowers) of Scutellaria baicalensis

Baicalin• The dried root of Baikal skullcap

( Scutellaria baicalensis ) has been historically and widely used in traditional Eastern medicine. Modern science proved that baicalin is the major bioactive

• Baicalin, a flavonoid found in several species in the genus Scutellaria , has been regarded as a potent anticancer agent

• Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States

• Surgery,• radiation therapy,• chemotherapy, • and targeted therapy are the most common types of cancer treatment. However, they might cause severe side effects in patients

• Fatigue, a common early and chronic side effect of irradiation, was reported in up to 80% of patients during radiation therapy and 30% of follow-up visits .The incidence of chemotherapy-induced nausea and vomiting (CINV) in patients was 59.7% within 24 hours after treatment. And the incidence of delayed-CINV was 22.9% in patients who experienced neither vomiting nor nausea during the first 24 hours post-chemotherapy. Thus, it is important to find an alternative cancer treatment with fewer adverse side effects.

• Baicalin is a flavonoid found in the Chinese herb Scutellaria baicalensis (also known as Baikal skullcap). Baicalein is the aglycone of baicalin. Baicalin has been applied in pharmaceuticals, food and cosmetics industries. Different extraction methods are employed to isolate baicalin from Scutellaria baicalensis.

Extraction

• are two most widely used extraction methods

• Different extraction methods are employed to isolate baicalin from Scutellaria baicalensis.

• heat reflux extraction (HRE)• ultrasound-assisted extraction (UAE)

Heat reflux extraction (HRE)

• HRE is a conventional extraction method which is versatile but time consuming

ultrasound-assisted extraction (UAE)

• Compared with HRE, UAE reduced the extraction time, the extraction temperature, and the solvent consumption

• UAE is considered as an economical alternative to replace traditional extraction methods

• Previous studies have revealed that UAE achieved superior yields of baicalin and had the prospects to be applied in the industrial production of baicalin

• One of the studies illustrated that the extraction of baicalin was most efficient at temperatures of 60°C, with ethanol concentration of 40% (v/v)

• Combinatorial use of HRE with UAE shows higher yield rate and efficiency compared with the use of HRE or UAE alone.

• Therefore, the combinatorial use of HRE with UAE is also very promising for the commercialized manufacture of natural compounds in the future (e.g. baicalin)