Baikal skullcap (Scutellaria baicalensis Georgi) – promising source of potential therapeutic agents for COVID 19 (SARS-CoV-2)

 

Bokov D.O.1,2*, Bobkova N.V.1, Sergunova E.V.1, Chevidaev V.V.1, Kakhramanova S.D.1, Zhilkina V.Yu.3, Mustafakulov B. F.1, Klyukina E.S.1, Selifanov A.V.2, Bondar A.A.1,

Evgrafov A.A.1, Yakubovich L.M.1, Kuleshova E.S.1, Gildeeva G.N.1, Smolyarchuk E.A.1, Luferov A.N.1, Samylina I.A.1, Krasnyuk I.I.1 (junior), Bessonov V.V.2,3

1Sechenov First Moscow State Medical University (Sechenov University),

8, Trubetskaya St., bldg. 2, 119991, Russian Federation.

2Federal Research Center of Nutrition, Biotechnology and Food Safety,

2/14, Ustyinsky pr., Moscow, 109240, Russian Federation.

3Рeoples’ Friendship University of Russia (RUDN University),

6, Miklukho-Maklaya Street, Moscow, 117198, Russian Federation.

*Corresponding Author E-mail: fmmsu@mail.ru

 

ABSTRACT:

Baikal skullcap (Scutellaria baicalensis Georgi) is a medicinal plant with many pharmacological properties. Modern phytochemical analysis has shown that S. baicalensis roots contains many groups of biologically active compounds (BAC), of which flavonoids are its main components, and baicalein is the most important of them. These BAC are the basis for the pharmacological action of S. baicalensis. Pharmacological studies have shown that S. baicalensis has a wide range of pharmacological activities, including antiviral effects, as well as anti-inflammatory, antibacterial, anti-cancer, liver protection, etc. S. baicalensis BAC may have a potential therapeutic effect against COVID-19, due to baicalin and baicalein content. The exact therapeutic effects have yet to be determined in clinical trials; this is a topic for future research. Thus, the extract of the roots of S. baicalensis, baicalein may become a promising therapeutic drug for the treatment of SARS-CoV-2.

 

KEYWORDS: Baikal skullcap, Scutellaria baicalensis, Baicalein, Baicalin, Scutellarein, Oroxylin, Wogonin.

 

 


 

INTRODUCTION:

Baikal skullcap (Scutellaria baicalensis Georgi, Fig. 1) –  a herbaceous perennial with a short many-headed rhizome, passing into a thick rod root of the Lamiaceae family; distributed in the Russian Federation in Primorye, Priamurye, Transbaikalia, also grows in Mongolia and northern China, Korea.1,2

 

Figure 1: Baikal skullcap (Scutellaria baicalensis Georgi).

 

In the Russian Federation, pharmacopoeial article 42-453-91 regulated the quality of crude herbal drugs – the roots of Scutellariae baicalensis or Scutellariae baicalensis radix. Tincture was obtained from S. baicalensis roots, which was used as a hypotensive agent for hypertension and as a sedative for cardiovascular neurosis. A monograph on the S. baicalensis roots is included in the European Pharmacopoeia 10th Edition.3 The raw material base in the Russian Federation is represented by wild-growing and cultivated plants.

 

The aim of the study was to conduct a complete pharmacognostic review of the S. baicalensis roots  and to evaluate prospects for creating drugs based on its extract.

 

MATERIALS AND METHODS:

For obtaining comprehensive data for the chemical composition of S. baicalensis roots, extracts, main compound and its pharmacological, instrumental analysis different electronic sources and databases were analyzed. They are Web of Science, Scopus, PubMed, E-Library, search engines (Google Scholar); we have analyzed all available sources.

 

RESULT AND DISCUSSIONS:

S. baicalensis is one of the most widely used medicinal plants of traditional Chinese medicine. Its roots (Huangqin) are used as antitumor, anti-inflammatory, antiviral and antibacterial agents in the treatment of infections of the gastrointestinal and respiratory tracts. It is used to detoxify, lower total cholesterol and blood pressure.4 Huangqin is officially registered in the Chinese Pharmacopoeia.5

 

The underground parts of S. baicalensis contain flavonoids (up to 10%): baicalein (up to 5%), baicalin (up to 9%), scutellarin, hydrolyzed into glucuronic acid, and aglycones: baicalein and scutellarein, oroxylin, wogoside up to 4%, wogonin up to 0.7%, etc .; tannins (up to 2.5%); essential oil; resins, steroids (sitosterol, stigmasterol, etc.), coumarins.1,6

 

Biologically active compounds (BAC) from the S. baicalensis root exhibit quite diverse pharmacological effects. A large number of studies are devoted to the study of the biological activity of S. baicalensis. BAC affect the central nervous system (show sedative, hypotensive, anticonvulsant effects), are useful for the liver (show hepatoprotective and antioxidant activity), reduce inflammation processes, inhibit the growth of pathogenic microorganisms (bacteria, viruses), have a cytotoxic effect on various tumor cell lines and        others.7-32 Baikalin, baikalein, oroxylin A and wogonin are the main biologically active compounds of S. baicalensis (Fig. 2).

 

Figure 2: Main biologically active compounds (flavonoids) of S. baicalensis.

 

It is noteworthy that S. baicalensis extracts exhibit a wide spectrum of antiviral activity, including H1N133, ZIKA34, DENV35 and HIV36. In addition, in a retrospective multicenter study it was confirmed that extracts of S. baicaleinsis have more pronounced antiviral effects and greater clinical efficacy than ribavirin.37 Several preparations based on extracts as well as individual compounds derived from S. baicalensis are officially approved in China for the treatment of viral infections: “Baicalein” (for the treatment of hepatitis in capsules) and “Huangqin” (for the treatment of upper respiratory tract infections in tablets). In China, the production of skullcap root extract on an industrial scale is organized. Most of the biologically active compounds in S. baicaleinsis are flavonoids; these include baicalin, baicalein, wogonin, and oroxylin A.38 It has also been reported that flavonoids from other plants have some inhibitory effect on SARS and MERS-CoV 3CLpro.39,40 Many flavones have similar activities, such as morin (2’,3,4’5,7-Pentahydroxyflavone) is a natural flavonoid found most commonly in guava, almonds, onion, strawberry, kiwi and also has antiviral properties.41,42

 

The work43 studied the anti-SARS-CoV-2 activity of 70% ethanol extract of S. baicalensis and its components. It was found that the ethanol extract of S. baicalensis inhibits the activity of SARS-CoV-2 3CLpro, and the most active ingredient, baicalein, exhibits an IC50 of 0.39 μM. In addition, the ethanolic extract of S. baicalensis effectively inhibits the replication of SARS-CoV-2 in cell experiments. When carrying out molecular docking, the inhibitory activity of the components of the S. baicalensis extract was established. Baicalein binds well at the binding site of the substrate SARS-CoV-2 3CLpro with its 6-OH and 7-OH-groups; a hydrogen bond is formed with the carbonyl group L141 and the basic amide group G143. In addition, the carbonyl group of baicalein is linked to the main amide group E166. Catalytic residues (residues that make up the catalytic center) H41 and C145 are completely blocked by baicalein, which explains its inhibitory effect. Since the 7-OH group in baicalin is in close contact with the protein, there may not be enough space for glycosyl modification, which explains the low activity of baicalin.

 

Using RT-qPCR, it was found that S. baicalensis extract and baicalein inhibit the replication of SARS-CoV-2 in Vero cells. An ethanol extract of S. baicalensis effectively inhibited the development of the virus with an EC50 of 0.74 μg/ml with low cytotoxicity (SI> 675.68). Baicalein inhibits SARS-CoV2 replication with an EC50 of about 17.6 μM and a SI> 2.8. The high activity of the crude S. baicalensis extract in antiviral assay implies that it can also interact with other viral or host targets in addition to inhibiting SARS-CoV-2 3CLpro43. Anti-SARS-CoV-2 3CLpro activity (inhibition of 3C-like protease in vitro) of S. baicalensis and its ingredients (baicalein) was proved. And therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro was discussed and identified.44-47

 

Baicalin and baicalein have pronounced antiviral properties; research in the technology of their isolation is urgent. It is known from the literature that the type of extractant, temperature and extraction time have a very strong effect on the qualitative and quantitative composition of the obtained extract.48-50 This is due to the presence of an active enzyme beta-glucuronidase in the cells of the skullcap root, which, when wetted with an extractant containing water, begins to actively hydrolyze baicalin to its aglycone (baicalein) and glucuronic acid.51 Researchers from Belgorod State University studied the kinetics of baicalin hydrolysis during its extraction from S. baicalensis roots using 43 and 72% ethanol. It was found that the reaction of baicalin hydrolysis is described by the first-order kinetic equation lnC = f (t); the half-life of baicalin in 43% ethanol is 4.6 ± 0.5 hours, in 72% ethanol –  42.3 ± 1.8 hours. The values ​​of the half-life of baicalin show that to obtain an extract with a maximum baicalin content and a minimum baicalein content, it is advisable to use the fast extraction technology (within 1-2 hours), as well as to use 70–80%. To isolate baicalein, infusion should be applied for at least 12 hours and 30-60% ethanol should be used.52 Further studies of enzymatic hydrolysis (HG-5 enzyme) during the extraction of baicalin are carried out and important for determining optimal extraction process.53

 

The most suitable dosage form for the herbal extract based on S. baicalensis roots is a hard gelatin capsule. They provide a gentle technological mode (it is possible to encapsulate the extract unchanged without adding a significant amount of auxiliary substances, without subjecting it to wet granulation, heat, pressure, etc.).

 

Various HPLC procedures can be used to assess the quality of extracts and to assess the pharmacokinetic parameters of baicalin and baicalein. Thus, an HPLC-MS/MS method was developed for the determination of baicalin, baicalein, oroxylin A, and wogonin in rat plasma. Liquid extraction was carried out with 2- (3,4-dimethoxyphenyl)-5,7-dihydroxychromen-4-one as an internal standard. Chromatographic conditions were as follows: Atlantis C18 column, isocratic mobile phase (methanol and 0.1% formic acid – 60:40, v / v), analysis time – 7 min. Analytes were detected using tandem mass spectrometry with electrospray ionization in multiple reaction monitoring (MRM) mode.54

 

There are also a number of techniques developed for pharmacokinetic studies.55-60 An HPLC-UV technique with isocratic elution was developed for the simultaneous determination of baicalin, baicalein, wogonin, and wogonoside. Chromatographic analysis was carried out on a YMC Pack Pro C8 column (150 × 4.6 mm, 2,3 μm) with a mobile phase of 0.1% formic acid: acetonitrile (70: 30, v/v) at a flow rate of 1.0 ml/min, and UV detection at 280 nm. This method has been successfully applied for the analysis of marker compounds and for quality control of the extract of S. baicalensis roots.61 There are also other effective procedures for HPLC-UV62-63 and HPLC-MS64-65 analysis of these flavonoids in S. baicalensis  root extracts.

 

At the moment, many issues related to the use of S. baicalensis root extract remain under development and discussion. It is necessary to create up-to-date regulatory documentation that would allow assessing the quality of both medicinal plant raw materials and preparations based on it. This fact is confirmed by studies from various countries that are engaged in pharmacognostic studies of medicinal plant materials.66-78

 

CONCLUSION:

It should be noted that the development of the technology of hard gelatin capsules with S. baicalensis root extract produced from imported or Russian origin raw materials seems to be very relevant. Capsules with dry ethanol (30-60%) extract with a high content of baicalein can be proposed as an effective drug for the prevention and treatment of coronavirus infection. Many variants of HPLC methods have been developed and validated both for assessing the quality of the extract itself and for conducting pharmacokinetic studies. They can be successfully used in the control of these dosage forms.

 

CONFLICTS OF INTEREST:

None.

 

AUTHOR’S CONTRIBUTIONS:

Authors contributed equally to this work.

 

REFERENCES:

1.      WHO monographs on selected medicinal plants. “Radix Scutellariae”; Vol. 3. Geneva: World Health Organization. 2007; 313-327.

2.      Manyakhin AYu, Zorikova SP, Zorikova OG. Dynamics of flavonoids accumulation and distribution in the baikal scullcap (Scutellaria baicalensis Georgi) organs. Bulletin of KrasSMU. 2009; 11: 79-83

3.      European Pharmacopoeia 10th Edition (EP)

4.      Wang ZL, Wang S, Kuang Y, Hu ZM, Qiao X, Ye M. A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol. 2018; 56(1): p. 465 465-484.

5.      Chinese Pharmacopoeia. 2015 edition. Chinese Pharmacopoeia Commission. Chinese pharmacopoeia. China Medical Science Press: Beijing, China

6.      Olennikov DN, Chirikova NK, Tanhaeva LM. Phenolic compounds of Scutellaria baicalensis (Scutellaria baicalensis Georgi). Khimija Rastitel’nogo Syr’ja. 2009; (4): 89-98.

7.      Ikezoe T, Chen SS, Heber D, Taguchi H, Koeffler HP. Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. T. Ikezoe. Prostate. 2001; 49: 285-292.

8.      Huang WH, Chien PY, Yang CH, Lee AR. Novel synthesis of flavonoids of Scutellaria baicalensis G EORGI. Chemical and Pharmaceutical Bulletin. 2003; 51(3): 339-340.

9.      Ciesielska E, Gwardys A, Metodiewa D. Anticancer, antiradical and antioxidative actions of novel Antoksyd S and its major components, baicalin and baicalein. Anticancer Res. 2002; 22(5): 2885-2891.

10.   Ciesielska E, Wolszczak M, Gulanowski B, Szulawska A, Kochman A, Metodiewa D. In vitro antileukemic, antioxidant and prooxidant activities of Antoksyd S (C/E/XXI): a comparison with baicalin and baicalein. In Vivo. 2004; 18(4): 497-503.

11.   Lin XC, Liu XG, Chen XW, Chen WZ, Liang NC. Inhibitory effect and its kinetic analysis of baicalein on recombinant human protein kinase CK2 holoenzyme. Ai Zheng. 2004; 23(8): 874-878.

12.   Chen YJ et al. Baicalein triggers mitochondria-mediated apoptosis and enhances the antileukemic effect of vincristine in childhood acute lymphoblastic leukemia CCRF-CEM Cells. Evid Based Complement Alternat Med. 2013; 2013: 124747.

13.   Bie B et al. Baicalein, a natural anti-cancer compound, alters microRNA expression profiles in Bel-7402 Human Hepatocellular Carcinoma Cells. Cell Physiol Biochem. 2017; 41(4):  1519-1531.

14.   Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review. Brain Sci. 2018; 8: 104. https://doi.org/10.3390/brainsci8060104

15.   Qasim MT, Al-Mayali HK. Investigate the relation between Baicalin effect and Gene expression of LH, FSH, Testosterone in male rats treated with Gemcitabine drug. Research Journal of Pharmacy and Technology. 2019; 12(9): 4135-4141.

16.   Shi, H. et al. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice. Scientific Reports, 2016; 6:  35851.

17.   Li C, Lin G, Zuo Z. Pharmacological effects and pharmacokinetics properties of Radix Scutellariae and its bioactive flavones. Biopharmaceutics & Drug Disposition. 2011; 32(8): 427-445.

18.   Kowalczyk E, Krzesiński P, Kura M, Niedworok J, Kowalski J, Błaszczyk J. Pharmacological effects of flavonoids from Scutellaria baicalensis. Przeglad Lekarski. 2006; 63(2): 95-96.

19.   Yoon SB et al. Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS-activated RAW 264.7 macrophages. Journal of Ethnopharmacology. 2009; 125(2): 286-290.

20.   Zhang XW et al. Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells. Shen. Pharm Biol. 2011; 49:  256-261.

21.   Gao Z, Huang K,  Xu H. Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells. Pharmacological Research. 2001; 43(2): 173-178.

22.   Shao ZH et al. Extract from Scutellaria baicalensis Georgi attenuates oxidant stress in cardiomyocytes. Journal of Molecular and Cellular Cardiology. 1999; 31(10): 1885-1895.

23.   Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochimica et Biophysica Acta (BBA)-General Subjects. 1999; 1472(3): 643-650.

24.   Gasiorowski K, Lamer-Zarawska E, Leszek J, Parvathaneni K, Yendluri BB, Blach-Olszewska Z, Aliev G. Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?  CNS Neurol Disord Drug Targets. 2011; 10;  184-191.

25.   Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev. 2009; 35:  57-68.

26.   Kumagai T, Muller CI, Desmond JC, Imai Y, Heber D, Koeffler HP. Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Leuk. Res. 2007; 31: 523-530.

27.   Choi J et al. Flavones from Scutellaria baicalensis Georgi attenuate apoptosis and protein oxidation in neuronal cell lines. Biochimica et Biophysica Acta (BBA)-General Subjects. 2002; 1571(3): 201-210.

28.   Himeji M et al. Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell. Cancer Lett. 2007; 245:  269-274.

29.   Huang ST et al. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine. 2010; 17:  47-54.

30.   Hui KM, Huen MS, Wang HY, Zheng H, Sigel E, Baur R, Xue H. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochemical Pharmacology. 2002; 64(9): 1415-1424.

31.   Park HG et al. Anticonvulsant effect of wogonin isolated from Scutellaria baicalensis. European Journal of Pharmacology. 2007; 574(2-3): 112-119.

32.   Huang RL et al. Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis. Planta Medica. 2000; 66(08): 694-698.

33.   Ji S et al. Anti -H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis. J Ethnopharmacol. 2015; 176: 475-84.

34.   Oo A et al. Baicalein a nd baicalin as Zika virus inhibitors. Arch Virol. 2019; 164(2): 585 -593.

35.   Zandi K et al. Extract of Scutellaria baicalensis inhibits dengue virus replication. BMC Complement Altern Med. 2013. 13: 1-10.

36.   Zhang  X, Tang X, Chen H. Inhibition of HIV replication by baicalin and S. baicalensis extracts in H9 cell culture. Chin Med Sci J. 1991; 6(4): 230-2.

37.   Lin H et al. Efficacy of Scutellaria baicalensis for the treatment of hand, foot, and mouth disease associated with encephalitis in patients infected with EV71: a multicenter, retrospective analysis. Bio Med Res Int. 2016 Article ID 5697571.

38.   Qiao X et al. A targeted strategy to analyze untargeted mass spectral data: Rapid chemical profiling of Scutellaria baicalensis using ultra ultra-high performance liquid chromatography coupled with hybrid quadrupole o rbitrap mass spectrometry and key ion filtering. J Chromatogr A. 2016; 1441: 83-95.

39.   Jo S et al. Inhibition of SARS SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem. 2020; 35(1): 145-151.

40.   Jo S et al. Characteristics of flavonoid s as potent MERS MERS-CoV 3C 3C-like protease inhibitors. Chem Biol Drug Des. 2019; 94(6): 2023-2030.

41.   Rithiga SB, Shanmugasundaram S. Virtual Screening of Pentahydroxyflavone–A Potent COVID-19 Major Protease Inhibitor. Asian Journal of Research in Pharmaceutical Sciences. 2021; 11(1): 7-14.

42.   Shanmugapriya E, Ravichandiran V, Aanandhi MV. Molecular docking studies on naturally occurring selected flavones against protease enzyme of Dengue virus. Research J. Pharm. and Tech. 2016; 9(7): 929-932.

43.   Liu H et al. Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro. Journal of Enzyme Inhibition and Medicinal Chemistry. 2021; 36(1): 497-503.

44.   Song J et al. The comprehensive study on the therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro. Biochemical Pharmacology. 2021; 183: 114302.

45.   Huang S et al. Baicalein inhibits SARS-CoV-2/VSV replication with interfering mitochondrial oxidative phosphorylation in a mPTP dependent manner. Signal Transduction and Targeted Therapy. 2020; 5(1): 1-3.

46.   Udrea AM, Mernea M, Buiu C, Avram S. Scutellaria baicalensis Flavones as potent drugs against acute respiratory injury during SARS-CoV-2 Infection: Structural Biology Approaches. Processes. 2020; 8(11): 1468.

47.   Su H, Yao S, Zhao W, Li M, Liu J, Shang W, Xu Y. Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro. BioRxiv. 2020. https://doi.org/10.1101/ 2020.04.13.038687

48.   Yu C et al. Different extraction pretreatments significantly change the flavonoid contents of Scutellaria baicalensis. Pharm Biol. 2013; 51(10): 1228-1235.

49.   Bhusari S, Morey S, Nikam K, Wakte P. Comparative Evaluation of Baicalein from Oroxylum indicum by using Conventional and Non-Conventional Extraction Methodology. Research Journal of Pharmacy and Technology. 2019; 12(4): 1817-1822.

50.   Li JH, Wang LS, Zou JM. Study on degradation of baicalin by endogenous enzymes in water extraction of Scutellaria baicalensis. Chin Trad Herb Drugs. 2009; 40: 397-400.

51.   Sasaki K et al. Molecular characterization of a novel beta- glucuronidase from Scutellaria baicalensis Georgi. J Biol Chem. 2000; 275: 27466-27472.

52.   Boyko NN, Pisarev DI, Zhilyakova ET, Maljutina AY, Novikov OO, Bocharnikova MA. Study of baicalin hydrolysis kinetics in the process of its extraction from Scutellaria baicalensis Georgi roots. Farmatsiya i Farmakologiya. 2019; 7(3): 129-137.

53.   Ma XD et al. Application of enzyme-assisted extraction of baicalin from Scutellaria baicalensis Georgi. Preparative Biochemistry and Biotechnology. 2020; 1-11.

54.   Kim YH et al. Liquid chromatography with tandem mass spectrometry for the simultaneous determination of baicalein, baicalin, oroxylin A and wogonin in rat plasma. Journal of Chromatography B. 2006; 844(2): 261-267.

55.   Kotani A, Kojima S, Hakamata H, Kusu F. HPLC with electrochemical detection to examine the pharmacokinetics of baicalin and baicalein in rat plasma after oral administration of a Kampo medicine. Analytical Biochemistry. 2006; 350(1): 99-104.

56.   Kim YH et al. Pharmacokinetics of baicalein, baicalin and wogonin after oral administration of a standardized extract of Scutellaria baicalensis, PF-2405 in rats. Archives of Pharmacal Research. 2007; 30(2): 260.

57.   Tong L, Wan M, Zhang L, Zhu Y, Sun H, Bi K. Simultaneous determination of baicalin, wogonoside, baicalein, wogonin, oroxylin A and chrysin of Radix scutellariae extract in rat plasma by liquid chromatography tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2012; 70: 6-12.

58.   Wang C et al.Retention mechanism of pH‐peak‐focusing in countercurrent chromatographic separation of baicalin and wogonoside from Scutellaria baicalensis Georgi. Journal of Separation Science. 2020; 43(19): 3806-3815.

59.   Feng J et al. Simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in rat plasma by liquid chromatography-tandem mass spectrometry and application in pharmacokinetic studies after oral administration of traditional Chinese medicinal preparations containing scutellaria–coptis herb couple. Journal of Pharmaceutical and Biomedical Analysis. 2010; 53(3): 591-598.

60.   Lai MY et al. Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats. Journal of Pharmacy and Pharmacology. 2003; 55(2): 205-209.

61.   Islam MN, Chung HJ, Kim DH, Yoo HH. A simple isocratic HPLC method for the simultaneous determination of bioactive components of Scutellariae radix extract. Natural Product Research. 2012; 26(21): 1957-1962.

62.   Sagara K, Ito Y, Oshima T, Misaki T, Murayama H, Itokawa H. Simulatneous determination of baicalein, wogonin, oroxylin-A and their glucuronides in scutellariae radix by ion-pair high-performance liquid chromatography. Journal of Chromatography A. 1985; 328: 289-297.

63.   Yang LX et al. Determination of flavone for Scutellaria baicalensis from different areas by HPLC. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi= China Journal of Chinese Materia Medica. 2002; 27(3): 166-170.

64.   Li HB, Jiang Y, Chen F. Separation methods used for Scutellaria baicalensis active components. Journal of Chromatography B. 2004; 812(1-2): 277-290.

65.   Han J, Ye M, Xu M, Sun J, Wang B, Guo D. Characterization of flavonoids in the traditional Chinese herbal medicine-Huangqin by liquid chromatography coupled with electrospray ionization mass spectrometry. Journal of Chromatography B. 2007; 848(2): 355-362.

66.   Jaiswal S, Chavhan SA, Shinde SA, Wawge NK. New Tools for Herbal Drug Standardization. Asian J. Res. Pharm. Sci. 2018; 8(3): 161-169.

67.   Ekka NR, Namdeo KP, Samal PK. Standardization Strategies for Herbal Drugs-An Overview. Research J. Pharm. and Tech. 2008; 1(4): 310-312.

68.   Bokov DO, Nizamova LA, Morokhina SL et al. Pharmacognostic studies of Origanum L. species Medicinal plant raw materials. Research Journal of Pharmacy and Technology. 13(9): 4365-4372.

69.   Sukmana BI, Edyson, Thahir H, Achmad H, Huldani, Bokov DO. Research review on secondary metabolite compounds of Mangifera casturi bark and their functions. International Journal of Pharmaceutical Research. 2020; 3(12): 2155-2161.

70.   Zhilkina V, Sachivkina NP, Ibragimova AN, Kovaleva TY, Molchanova MA, Radeva DV. Methods for the identification and quantitative analysis of biologically active substances from vitamin plants raw material. FEBS Open Bio. 2019; 9(S1): 285-286.

71.   Vatnikov Y, Rudenko P, Shopinskaya M et al. Effectiveness of biologically active substances from Hypericum perforatum L. in the complex treatment of purulent wounds. International Journal of Pharmaceutical Research. 2020; 4(12): 1108-1117.

72.   Bokov DO. Standardization of snowdrop (Galanthus L.) herbal pharmaceutical substances by ultraviolet-spectrophotometry. Asian J Pharm Clin Res. 2018; 11(10): 207-211.

73.   Vatnikov Y, Shabunin S, Karamyan A et al. Antimicrobial activity of Hypericum perforatum L. International Journal of Pharmaceutical Research. 2020; 12: 723-730.

74.   Nishith MC, Venkatesh MP. Herbal Drug Regulatory Landscape: Key Comparison between Russia and India. Research J. Pharm. and Tech. 2019; 12(12): 6153-6156.

75.   Mustafa A, Alvi AI, Siddiqui ZA, Meena RP. Heavy metals determination in Microwave digested aqueous extracts of fresh and market samples of some Plant origin drugs with reference to their preliminary comparative physico-chemical evaluation. Res. J. Pharmacognosy and Phytochem. 2021; 13(1): 11-17.

76.   Sindhu RK, Kaur P. Regulatory requirements and stability testing of ethnomedicinal plant products. Research J. Pharm. and Tech. 2020; 13(3): 1538-1542.

77.   Ye F et al. Quality evaluation of commercial extracts of Scutellaria baicalensis. Nutrition and Cancer. 2004; 49(2): 217-222.

78.   Hu LQ et al. Preliminary study on standardization of production and processing of Scutellaria baicalensis pieces. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi= China Journal of Chinese Materia Medica. 2019; 44(15): 3281-3286.

 

 

 

Received on 16.03.2021      Revised on 14.02.2025

Accepted on 09.12.2025      Published on 13.01.2026

Available online from January 17, 2026

Research J. Pharmacy and Technology. 2026;19(1):33-37.

DOI: 10.52711/0974-360X.2026.00005

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