Baikal skullcap

Scutellaria baicalensis (of the Labiatae family) is a plant sometimes referred to as Huang qin or Scutellariae radix (when referring to the root) and has usage in Traditional chinese medicine (TCM) for the treatment of cardiovascular disease,^[1] bleeding disorders (hematemesis, hematuria, and metrorrhagia),^[2]

The related plant, Scutellaria lateriflora, is commonly referred to as Skullcap; this term is sometimes also applied to Scutellaria baicalensis along with the names 'Golden Root' (this name also applies to Rhodiola Rosea by pure chance).^[3]

Scutellaria baicalensis is a component of various combination therapies (from TCM) including Ger-Gen-Chyn-Lian-Tang (rhizome of Coptidis chinensis paired with the roots of Pueraria Lobata, licorice, and scutellaria baicalensis),^[4] Soshiho-tang (Bupleurum falcatum, licorice, panax ginseng, ginger, ziziphus jujuba, and Pinellia ternata with scutellaria baicanelsis),^[5] and shuanghuanglian (forsythiae fruits and honeysuckle with scutellaria baicanelsis).^[6]

Scutellaria baicalensis is a traditional chinese medicine used for general preventative health purposes, with a bit more focus towards cardiovascular and bleeding disorders as well as neuroprotective/cognitive enhancing properties

• Baicalin (Baicalein-7-glucuronide)^[7][8] and its aglycone baicalein, as well as another glycoside known as baicalein-7-O-glucoside^[9]
• Wogonoside (wogonin-7-glucuronide) and its aglycone Wogonin^[8] as well as another glycoside known as Wogonin-5-O-glucoside^[9]
• Oroxylin A (5,7-dihydroxy-6-methoxyflavone)^[10] and its 7-O-glucoside^[9]
• Neobaicalein
• Scutellarin and Isoscutellarein^[11]
• Chrysin^[12]
• Viscidulin I and Visdulin III^[12]
• Skullcapflavone I^[13] and II^[12]
• (2R,3R)-2′,3,5,6′,7-pentahydroxyflavanone^[14][15]
• (2S)-5,7,2′,6′-tetrahydroxyflavanone^[12]
• (2S)-5,7-dihydroxy-6-methoxyflavanone^[12]
• 5,7,2'-trihydroxy-6,8-dimethoxyflavone (K36)^[12]
• 6,2′-dihydroxy-5,7,8,6′-tetramethoxyflavone^[12]
• 5,7,4′-trihydroxy-8-methoxyflavone ^[12]
• Apigenin (as 6-C-glucoside 8-C-arabinoside)^[11]
• Luteolin and 6-hydroxyluteolin^[11]
• Carthamidin (as 7-O-glucuronic acid) and Isocarthamidin-7-O-glucuronic acid^[11]

The flavonoids wogonin and baicalein (as well as their glycosides) are commonly seen as the main active ingredients of scutellaria baicalensis, although there are some other unique flavonoids (namely Oroxylin A and K36) that underlie some of the benefits of this plant. Most other bioactives are either in small quantities and not potent enough to be active, or are common structures found in many plants

The main bioactives are highly present in the roots while not in high levels in the aerial parts (stem and leaves).^[16][17][11]

Due to having higher concentrations of the unique bioactives, the main part of the plant that is consumed is the root extract

Some plants in traditional chinese medicine are recommended as decoctions (extracts via liquid) involving a brief soaking period followed by boiling or decocting, with the liquid result being drunk as tea.^[9] Ideally, for best preparation of scutellaria baicalensis roots (to reach highest levels of flavonoids extracted) it is soaked in 50°C water for 30 minutes in a herb:water ratio of 1:5-10, and optimum pH is slightly acidic (6.67).^[9]

The aforementioned optimal conditions have been noted to reduce the glycosides (to 1/70^th and 1/13^th for baicalin and wogonoside) while increasing levels of the aglycones by 3.5-fold (baicalein) and 3.1-fold (wogonin), due to removing the glucuronide attached to the aglycone.^[9]

Proper extractions can increase levels of the aglycones and reduce concentrations of the glycosides, which is due to removal of the glucuronide from the flavonoid

Baicalein itself appears to be well absorbed (P_app of 1.691+/-0.135x10^-5cm/s in a Caco-2 model^[18]) although it appears to be rapidly glucuronidated and the baicalein glucuronide is sent back into the lumen (to the basal side of the Caco-2 model).^[18] Wogonin and Oroxylin A have similarly good absorption initially,^[19] and when baicalein is glucuornidation and effluxed it is not reabsorbed.^[18]

Efflux of baicalein and other flavonoids (wogonin and oroxylin A) appear to involve MRPs^[20] and the inhibitor MK571 (MRP1 inhibitor) is able to block absorption.^[19] P-glycoprotein was not involved in the absorption of these flavonoids.^[19]

Although the flavonoids (baicalein most researched) appear to be very well researched, they are rapidly metabolized and then effluxed into the intestines and their metabolic products are not reabsorbed

Baicalin appears to involve intestinal microflora for its metabolism into baicalein (via removal of the glucuronide group), as decreasing intestinal microflora alters the kinetics of the flavonoid.^[21]

There may be some absorption of the glycoides (baicalin, wogonoside, etc.) in the colon after hydrolysis by intestinal bacteria

Administration of isolated flavonoids at 5mg/kg noted relatively quick absorption and peaks values, with T_max values being measured at 5.00m (baicalin), 12.0+/-10.4m (wogonin), and 4.33+/-1.15m (oroxylin A) and reaching respectively C_max values of 1.10+/-0.49µg/mL (baicalin), 0.57+/-0.14µg/mL (wogonin), and 0.24+/-0.08µg/mL (oroxylin A).^[22] While oroxylin A had a quick half-life (38.8m), the other two were more delayed (102-155m).^[22]

Administration of a mixture of flavonoids sees oroxylin A have an increase in overall AUC by 170% while the AUC values for baicalin and wogonin decrease by 24% and 11.6%.^[22] This is thought to be due to the enzymes of metabolism (glucuronidation) competing for substrate and possibly having less affinity for oroxylin A, as there was no apparent inhibition at the level of the transporter.^[22]

Although each flavonoid is absorbed on its own, it appears that ingesting multiple flavonoids will reduce the rate of metabolism (possibly via competitive means). Oroxylin A appears to have a greater AUC under these instances, perhaps due to less affinity for the enzymes (which would rather metabolize baicalin and/or wogonin)

Administration of the plant material as a decotion at 8mL/kg (baicalin at 21.1mg/mL, wogonoside at 1.88mg/mL, baicalein at 9.72mg/mL, wogonin at 8.22mg/mL, oroxylin A at 0.62mg/mL and chrysin at 0.23mg/mL) followed a bimodal absorption with a peak after 45 minutes (thought to be due to direct absorption) and then a lesser peak at 8-12 hours (possible related to colonic fermentation).^[23] The peaks reached in this study were recorded for baicalein (C_max of 2228+/-463ng/mL at a T_max of 0.23+/-0.09h), baicalin (13306+/-2626ng/mL at 0.30+/-0.07h), wogonoside (816.4+/-144.9ng/mL at 0.60+/-0.15h), wogonin (2526+/-378ng/mL at 0.33+/-0.20h), oroxylin A (471.6+/-115.4ng/mL at 0.20+/-0.07h), and chrysin (90.22+/-19.55ng/mL at 0.40+/-0.15h).^[23]

Other studies have confirmed somewhat similar peaks in the blood for the main three flavonoids following oral ingestion in rats^[24][25] including a standardized extract of PF-2405.^[26]

Ingestion of the root of the plant results in increases in serum levels of all measured bioactives, with the peaks for the flavonoids reaching the low micromolar (µM) range

Baicalein does not appear to undergo any hydroxylation of phase I metabolism in liver or intestinal microsomes.^[27]

At the same site that baicalin, wogonin, and oroxylin A are initially bound to their glycoside they can also be conjugated by 5'-diphospho-glucuronosyltransferase (UGT) or sulphotransferase (SULT) enzymes in the liver.^[27][18] Baicalin is most rapidly conjugated by UGT1A8 and 1A9, although all except 1A3 and 1A7 are active on converting baicalin to baicalin glucuronide.^[27]

The flavonoids appears to be readily glucuronidation, which constitutes the major pathway of metabolism

The rate of conjugation appears to be lesser when the three main flavonoids are coingested relative to when they are taken in isolation, which is thought to be due to competition by glucuronidation enzymes.^[22] It has been noted elsewhere (baicalin in isolation) that maximal rate of metabolism was at 10µM with higher concentrations having a lower rate, suggesting a saturation point.^[27]

As all three main flavonoids are glucuronidated, the rate of glucuronidation any individual flavonoid is lesser when a mixture of all of them are ingested

Baicalin is able to cross the blood brain barrier (injected dose of 24mg/kg) and concentrations detected in cerebrospinal fluid following this dose have reached 344.235+/-71.406μg/L (27% of serum concentration).^[28]

Baicalin in the blood can cross the blood brain barrier, although it does not appear to be at the same concentration in the brain and the blood

Oroxylin A appears to be able to inhibit the P-glycoprotein (P-gp) transporter in the range of 5-40μM and has shown efficacy at an oral intake of 50mg/kg to rats altering paclitaxel pharmacokinetics.^[29]

Oroxylin A, in higher oral doses, appears to be a P-glycoprotein inhibitor

Components of scutellaria baicanelsis are known to interact with adenosine monophosphate kinase (AMPK), a protein involved in energy metabolism and the main target of Berberine and Metformin.^[30] AMPK is regulated by both LKB1 (direct phosphorylation and ADP:ATP responsive)^[31] and CaMKKβ (intracellular calcium influx and ADP:ATP insensitive)^[32] proteins.

Baicalin (the glycoside) has been found to preserve the levels of hepatic AMPK when given intraperitoneally at 80mg/kg, which was credited to abolishing the weight gain on a high-fat diet (the high fat diet was able to reduce AMPK phosphorylation).^[33] AMPK has been found to be activated by baicalin in the concentration range of 5-10μM^[33] and appears to be due to CaMKKβ rather than LKB1^[34] similar to resveratrol,^[35] phosphorylation of AMPK has been noted at concentrations as low as 1µM (5µM similar potency) to around 4-fold control levels within an hour.^[34]

The activation of AMPK via baicalin does not appear to be associated with ROS production^[34] (producing ROS is known to activate AMPK^[36][37]) and both wogonin (in vitro)^[38] and oral ingestion of scutellaria baicalensis (10-100mg/kg in rats over four weeks)^[39] have been noted to increase AMPK phosporylation.

This activation of AMPK has been shown to be responsible for lipid and cholesterol lowering effects of baicalin.^[34][33]

Components of scutellaria baicalensis are known to activate AMPK, which may be a link between the lipid lowering and anti-obese actions of this plant

Baicalein appears to be a GABA_A receptor agonist, with the glycoside (Baicalin) having no such effect.^[40] Its potency is greater than that of chrysin^[40] and it has a K_i value of 5.69+/-0.95µM^[41] (IC₅₀ of 10.1+/-1.68μM^[12]). The glycoside, baicalin, has a weaker K_i value at 77.10+/-4.79µM and IC₅₀ above 100μM.^[41] Interestingly, baicalein may only significantly influence GABA_A receptors with α2 and α3 subunits^[42][43] which can explain anxiolytic properties and the lack of sedative properties.

Wogonin is also a GABA_A agonist^[44] with a K_i of 2.03+/-0.24µM at the benzodiazepine binding site.^[41]

Baicalin is active in inhibiting convulsion at an oral dose of 5mg/kg^[40] and wogonin at 5-10mg/kg.^[44] Both of which suggest that they are active following oral ingestion.

Baicalein and Wogonin are both potent GABA_A agonists, and can activate this receptor. This is thought to mediate some of the depressant and anxiolytic effects of scutellaria baicalensis

5,7,2'-trihydroxy-6,8-dimethoxyflavone (K36) is the most effective GABA_A ligand with a K_i of 6.05+/-0.63nM^[45] and appears to be a positive allosteric modulator at concentrations of 1nM (EC₅₀ of 24nM), although maximal stimulation of GABA_A receptors only reached 54+/-8% of that seen with diazepam (both at 300nM).^[45] Elsewhere, K36 has been found to potently outcompete flunitrazepam for binding to the benzodiazepine site with an IC₅₀ of 0.008+/-0.0002μM (8.0+/-0.2nM)^[12]

Other flavonoids with affinity for the GABA_A receptor include scutellarein which has a K_i for the GABA_A receptor of 12.00+/-1.27µM at the benzodiazepine binding site^[41] (IC₅₀ of 21.0+/-1.79μM^[12])

Beyond the two main flavonoids, K36 appears to be incredibly potent in both enhancing signalling through the benzodiazepine receptor while suppressing maximal signalling

Oroxylin A appears to be a GABA_A receptor antagonist (inhibiting the chloride influx^[40][46]) at the benzodiazepine binding site and can inhibit binding of flunitrazepam with an IC₅₀ of 1.09+/-0.07µM^[47] and elsewhere an IC₅₀ of 0.14+/-0.01µM has been noted;^[12] oral ingestion of 3.75-60mg/kg oroxylin A to rats was able to inhibit the effects of diazepam.^[47] It has elsewhere blocked the chloride influx induced by muscimol (GABA_A agonist)^[48][40] and by baicalein.^[40]

Oral ingestion of 50mg/kg oroxylin A has shown minor proconvulsive effects in a rat model (typical of GABA_A antagonists)^[40] and 5mg/kg oroxylin A has shown anti-amnesiac effects attributed to the GABA_A receptor antagonism.^[46]

Oroxylin A is a relatively effective GABA_A antagonist at the benzodiazepine binding site and has been confirmed to be active following oral ingestion, its properties oppose that of baicalein and wogonin

Oroxylin A has shown an ability to block the dopamine transporter (DAT) in a manner similar to methylphenidate, albeit with less potency (similar potency of oroxylin A to atomoxetine).^[49] And synthetic derivatives have been made (5,7-Dihydroxy-6-methoxy-4'-phenoxyflavone) with comparable potency than methylphenidate.^[50] This is thought to underlie the attention promoting effects observed at 5-10mg/kg oroxylin A (injections) that had a potency similar to 2mg/kg methylphenidate in spontaneous alterations^[49] while 1-5mg/kg was slightly less effective at reducing impulsiveness.^[49]

Oroxylin A appears to be a dopamine transport inhibitor, similar to methylphenidate (Ritalin) which is thought to underlie the attention-promoting effects

Despite inhibiting dopamine uptake, oroxylin A has failed to modify noradrenaline uptake.^[49]

No known interactions with adrenergic neurotransmission at this moment in time

Oroxylin A has been noted to increase CREB and BDNF phosphorylation in cognitively injured mice at 5mg/kg oral intake^[51] and mice with beta-amyloid induced memory impairments^[52] or to 400% of control mice (no cognitive impairment) at 50μM^[53] which is due to activating ERK1/2 (an MAPK),^[53][53] this is downstream of GABA_A antagonism, as it was mimicked by bicuculline, and blocked by inhibiting NMDA receptors.^[53][53]

Due to the above mechanisms, oroxylin A has been noted to stimulate neurogenesis in the hippocampus in a dose-dependent manner when administrated for 7-14 days to otherwise normal mice (5-10mg/kg), with 5mg/kg performing equally to 10mg/kg and 14 days not outperforming 7 days.^[54]

The inhibition of GABA_A receptors seen with oroxylin A seems to indirectly augment NMDA dependent signalling, which then increases the amount of neurogenesis that occurs. This has been confirmed in rodents following oral ingestion of low doses of this molecule

Baicalin can enhance neural stem/progenator cell production and hippocampal dependent neurogenesis in rats following cerebral ischemic injury when injected at 50mg/kg daily for three weeks,^[55] which is thought to be related to an upregulation of MASH1 expression at 7.5-30µM.

Heat Shock Protein 70 (HSP70) is an inducible HSP that exert protective effects in neurons^[56] with particular efficacy against ischemic damage,^[57][58] this neuroprotective property has been noted with baicalin at 200-300mg/kg^[59][60][61] and baicalin is known to preserve HSP70 concentrations during ischeia associated with a preservation of ERK phosphorylation (cytoprotective^[62][63]) and reducing the phosphorylation of p38 MAPK and JNK (positively mediates cell death^[64][63]) resulting in cytoprotective effects.^[61]

Microglia are neuronal support cells involved in the immune system that are able to become 'activated' via inflammatory signals^[65] and this inflammation is thought to at least contribute towards cognitive decline such as Parkinson's,^[66] Alzheimer's,^[67] and multiple sclerosis^[68] due to the neurotoxicity associated with chronic activation.^[69]

Oroxylin A is able to inhibit microglia activation (from LPS) in the concentration range of 10-100µM as assessed by nitric oxide secretion^[70][71] is able to prevent STAT1 activation (70-85% inhibition at 50µM) without affecting NF-kB translocation, ultimately resulting in less secretion of inflammatory cytokines.^[71] Wogonin is also able to suppress microglia activation, although via suppressing NF-kB at 50µM.^[72]

Oroxylin A and wogonin have been implicated in preventing inflammatory responses in brain cells, which are thought to underlie some of the neuroprotective effects

Reductions in microglia activation and the subsequent inflammation have been noted in vivo when rats are fed 100mg/kg of the extract daily during chronic LPS-injections.^[73]

Scutellaria baicalensis has shown anti-amnesiac and memory promoting properties against ibotenic acid (toxin that mimicks Alzheimer's^[74]) at 10-300mg/kg oral intake (30mg/kg being most effective),^[75] beta-amyloid proteins,^[52] chronic lipopolysaccharide infusion (100mg/kg of the herb daily, 200mg/kg ineffective),^[73] gamma irradiation (isolated baicalin),^[76] ischemia,^[77] and in animal models of aging (35-115mg/kg range).^[78][79][80] In regards to reversing age-related amnesia, scutellaria baicalensis (50-200mg/kg) is slightly more potent than the comparator of 200mg/kg piracetam over 47 days.^[80]

Scutellaria baicalensis appears to have anti-amnesiac properties that are quite general

One study assessing the anti-amnesiac properties of Oroxylin A against scopolamine conducted a test in otherwise normal young mice, and while 2.5-20mg/kg trended to improve cognition (passive avoidance) only 5-10mg/kg reached statistical significance.^[46]

Some evidence to support the usage of Oroxylin A in improving cognition in otherwise healthy and young rodents, suggesting nootropic effects

20mg/kg of baicalin to rats (prodrug for baicalein, a GABA_A agonist) has failed to significantly affect locomotor activity^[40] and 10mg/kg wogonin also appears to be ineffective.^[44] Even the potent GABA_A modulator K36 at 1-8mg/kg (injections) has failed to alter locomotion despite conferring anxiolytic properties.^[45]

Intracerebral injections of baicalein have shown sedative properties in augmenting sleep time (108-120% of control), while benzodiazepine antagonists failed to abolish the effects in one study^[81] yet were successful in preventing the increase in sleep time in the other study.^[82] Both slow-wave sleep and REM sleep appear to be increased with baicalin administration prior to dark phase sleep (nighttime sleeping).^[82]

Sleep induced in light phases (equivalent of daytime) seems to actually be hindered by baicalin, thought to be from interfering with an IL-1β induced slow wave sleep enhancement.^[82]

Baicalein has shown anxiolytic properties in a rat conflict test due to binding to the benzodiazepine binding site of the GABA_A receptor^[83]

GABA_A receptors with α2 and α3 subunits are implicated (as they are the target of baicalein^[42][43]).

In spontaneously hypertensive rats (also a model for attention deficits thought to be related to altered dopamine transportation^[84]) oroxylin A appears to improve attention^[48][49] thought to be related to its ability to block the dopamine transporter.^[49]

Oroxylin A may have attention-promoting properties due to its inhibition of the dopamine transporter, a mechanism similar to methylphenidate (ritalin)

Baicalin has been shown to stimulate nitric oxide production in isolated HUVECs (endothelial cells) via activating eNOS in the range of 50-200nM with 50nM outperforming 10nM bradykinin (comparator).^[1] Baicalein, wogonin, and wogonoside appear to be inactive on eNOS in the 10-200nM range,^[1] suggesting that the glucuronide group of baicalin is required.

This may be biologically relevant as some evidence suggest a hypothermic effect due to cutaneous vasodilatation in a dose-dependent manner.^[85]

Baicalin (the glycoside, aglycone is inactive) appears to be a potent eNOS inducer and potentially can increase nitric oxide. This may be relevant after oral ingestion due to the low concentration required

Components of scutellaria baicalensis have demonstrated lipid and cholesterol lowering effects secondary to AMPK activation in vitro.^[34][33]

May have lipid lowering properties in animals due to activation of AMPK, a known lipid lowering mechanism of action

Due to the ability of both Wogonin^[38] and Baicalin^[33] (as well as the whole plant extract^[39]) to activate AMPK, scutellaria baicalensis has some evidence investigating its interactions with glucose metabolism. This is since AMPK activation is inhernetly hypoglycemic^[30] and the molecular target of many anti-diabetic compounds (Metformin and Berberine in particular).

Scutellaria baicalensis may have anti-diabetic properties due to its ability to activate AMPK

In studies of diabetic mice, 10-100mg/kg of the plant extract (11.02% baicalin, 1.40% baicalein, and 0.39% wogonin) has been found to dose-dependently reduce circulating insulin concentrations over four weeks^[39] which has been replicated with 400mg/kg of the plant over the same timeframe with a potency nonsignificantly greater than 500mg/kg metformin.^[86]

50mg/kg of scutellaria baicalensis (20.46% baicalin, 0.93% baicalein, and 0.33% wogonin) or 5mg/kg of isolated baicalin have elsewhere failed to reduce blood glucose in diabetic rats^[87] although 400mg/kg appears to be as effective as the reference drug (500mg/kg metformin).^[86]

This plant may reduce blood glucose, although it appears to require a few weeks to be effective. It seems to be more effective in reducing insulin than in reducing glucose

PPARα is a target that regulates fatty acid synthesis and oxidation^[88] and are thought to be a druggable target to treat obesity,^[89] the activation of PPARα is known to be beneficial for obesity as it increases fatty acid oxidation while suppressing synthesis.^[90]

Scutellarin is able to suppress adipocyte differentiation at 100μM (but not 50μM) associated with downregulation of adipogenic transcription factors (PPARγ and C/EBPα, no influence on C/EBPβ) and upregulation of PPARα and no influence on PPARδ.^[91] Scutellarin was found to bind to PPARα, although its affinity was not determined.^[91] Wogonin has been found to also activate PPARα as well as AMPK.^[38]

It is possible that flavonoids in scutellaria baicalensis can activate a protein called PPARα and thus cause fat burning, but this is currently not well investgiated following oral ingestion (and occurs at fairly high concentrations)

Intraperitoneal injections of 80mg/kg baicalein daily for 16 weeks was able to inhibit the fat gain caused by a high-fat diet in rats, which is thought to be secondary to AMPK activation in the liver.^[33] In diabetic mice (db/db) given 10mg/kg or 100mg/kg of scutellaria baicalensis (11.02% baicalin) extract daily for four weeks, supplementation was able to dose-dependently reduce the observed weight gain,^[39] again thought to be due to AMPK activation.

Minimal evidence, but either isolated flavonoids or the root extract itself can reduce weight gain which is thought to be secondary to AMPK activation. No studies have yet assessed fat loss per se

PHA-activated PBMCs are significantly suppressed to near undetectable levels (1.9% of control) with 50-200µg/mL of the ethanolic extract.^[7]

Scutellaria baicalensis shows moderate anti-inflammatory effects on LPS-induced macrophage activation, with the ethanolic root extract (8.53% baicalin) reducing nitric oxide production to 8.85% of control at 800µg/mL and 54.6% at 200µg/mL (outperformed only by Schizonepeta tenuifolia).^[7] The water extract had minimal inhibition^[7] and has elsewhere shown a potency (50-400µg/mL) comparable to 25µM gallic acid.^[2]

Isolated compounds from this plant have inhibited LPS-induced macrophage activation, including baicalein (66.4+/-1µM), wogonin (45.3+/-0.2µM), and oroxylin A (58.2+/-0.6µM)^[3] with the latter also effective in other tissues via inhibition of NF-kB^[92][93] to near control levels in the range of 5-20µg/mL oroxylin A.^[94]

When looking at the mechanisms it appears that baicalein activates the estrogen receptor on macrophages^[95] similar to oroxylin A (in the range of 10nM to 10µM).^[96] When the estrogen receptor is activated on macrophages it causes antiinflammatory effects via suppressing NF-kB activation^[97] and the effects of both baicalein and oroxylin A are blocked when estrogen signalling is blocked.^[95][96]

Baicalein and Oroxylin A are both antiinflammatory agents on macrophages, and this appears to be secondary to them acting on the estrogen receptors and causing suppression of NF-kB activation

Baicalin is known to inhibit HIV replication^[98] with a potency in the range of 43.27-47.34μM^[99] and is more potent when bound to zinc (29.08-31.17μM).^[99]

Anti-bacterial effects from baicalin have been noted against Staphylococcus aureus induced pneumonia where the bacteria secreted α-Hemolysin (a polypeptide that aids in infection^[100][101]) is interfered with in vitro (IC₅₀ of 6.63μg/mL) and following injections of 25-100mg/kg baicalin alongside the bacteria in mice.^[102] It appears that baicalin can directly bind to α-Hemolysin in the latter's binding cavity which interfers with its ability to bind to cells, and may extend to wogonin (IC₅₀ of 10.27μg/mL) but not scutellarin.^[102]

An ethanolic extract of scutellaria baicalensis (5.7% baicalin) given to rats 48 hours prior to an allergic challenge (compound 48/80) at 280mg/kg bodyweight was able to exert a mild antiallergic action relative to control (about 6.6%)^[103] despite stronger actions in vitro where 1-100μg/mL caused a near halving of histamine release with most potency at 10μg/mL.^[103]

There appears to be a possible suppressive effect on histamine release with scutellaria baicalensis, although the current oral evidence in rats did not suggest a large degree of efficacy

An injection of 20mg/kg isolated wogonin appears to be more effective at reducing carrageenaan-induced paw edema (82.9%) than ibuprofen.^[3]

Scutellaria baicalensis (400mg/kg of 29.6% baicalin) in combination with the anti-diabetic drug Metformin (500mg/kg) in diabetic rats noted that all three groups (either drug in isolation plus the combination) were equally effective in reducing blood glucose and triglycerides over four weeks although they appeared to be additive in increasing pancreatic insulin concentrations and antioxidant status.^[86]

Although there is no evidence that Scutellaria baicalensis enhances the anti-diabetic effects of Metformin, it appears to aid with antioxidant status of diabetic rats and thus may be complementary

An ethanolic extract of Scutellaria baicalensis is able to induce relaxation in the corpus cavernosum in a concentration dependent manner reaching 89.85+/-9.97% relaxation at 300µg/mL.^[15] This is inhibited by nitric oxide and cGMP inhibitors, and is involved with potassium channels (regulator of blood flow in this tissue^[104] as channel openers cause relaxation^[105]) but independent of muscarininc and adrenergic receptors.^[15]