Tian Ma Gou Teng Pian

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral Baikal skullcap for allergic rhinitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Anxiety. Although there has been interest in using oral Baikal skullcap for anxiety, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Atherosclerosis. Although there has been interest in using oral Baikal skullcap for atherosclerosis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral Baikal skullcap for ADHD, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Bronchiolitis. Intravenous Baikal skullcap has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a combination of Baikal skullcap, forsythia, and honeysuckle, known as Shuang Huang Lian in traditional Chinese medicine, given intravenously, with or without antibiotics, decreases the duration of cough by about 1.5-2 days, the duration of wheezing by about 2 days, and the duration of hospitalization by about 2-3 days when compared with antibiotics alone in children with respiratory syncytial virus (RSV) infection. Baikal skullcap injection was administered as a 20 mL dose for patients under 6 months, a 40 mL dose for patients 7-36 months, or a 60 mL dose for patients older than 36 months (12613).
• Cancer. Although there has been interest in using oral Baikal skullcap for cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Diabetes. It is unclear if oral Baikal skullcap is beneficial in patients with diabetes. Details: A very small clinical trial in patients with uncontrolled diabetes taking metformin 500 mg daily shows that taking Baikal skullcap extract 3.52 grams in three divided doses daily for 8 weeks does not decrease levels of fasting glucose or insulin or improve levels of glycated hemoglobin (HbA1c) when compared with placebo. However, taking Baikal skullcap reduces blood glucose levels during an oral glucose tolerance test (OGTT) at 60 minutes, but not 120 minutes, when compared with placebo (101738). This study may have been inadequately powered to detect a difference between groups.
• Epilepsy. Although there has been interest in using oral Baikal skullcap for epilepsy, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hand, foot, and mouth disease. It is unclear if intravenous Baikal skullcap is beneficial in patients with hand, foot, and mouth disease. Details: Low-quality observational research in children hospitalized with severe hand, foot, and mouth disease has found that children who are given Baikal skullcap intravenously as a Tanreqing injection 0.3-0.5 mL/kg once daily have a shorter duration of fever, oral ulcers, and rash, as well as reduced viral load, when compared with those given ribavirin 10 mg/kg once daily (96281). The validity of these findings is limited by the retrospective nature of the study.
• Headache. Although there has been interest in using oral Baikal skullcap for headache, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hemorrhoids. Although there has been interest in using oral Baikal skullcap for hemorrhoids, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Hepatitis. Although there has been interest in using oral Baikal skullcap for hepatitis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• HIV/AIDS. Although there has been interest in using oral Baikal skullcap for HIV/AIDS, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Insomnia. Although there has been interest in using oral Baikal skullcap for insomnia, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Osteoarthritis. Oral Baikal skullcap has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific product (Limbrel, Primus Pharmaceuticals) that contains flavocoxid, a blend of Baikal skullcap extract and catechu flavonoid extract, 500 mg once or twice daily for up to 12 weeks reduces symptoms of osteoarthritis of the knee when compared with baseline. These studies found no significant difference between this combination product and naproxen 440 mg once daily to 500 mg twice daily for reducing symptoms (17030,18012,92776). However, in 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). See the Adverse Effects section for more information.
• Peyronie disease. It is unclear if oral Baikal skullcap is beneficial in patients with Peyronie disease. Details: Observational research has found that taking oral Baikal skullcap root extract 150 mL twice daily for 6 months is associated with reduced time to disease stabilization, with an average reduction of 5 months, when compared with no treatment. In addition, 17% of patients taking Baikal skullcap had pain resolution and only 33% required surgical correction, compared with 0% and 58%, respectively, of control patients. In patients requiring surgery, taking Baikal skullcap did not appear to affect resolution; however, the study may have been inadequately powered to detect a difference between groups (105867).
• Prostate cancer. Although there has been interest in using oral Baikal skullcap for prostate cancer, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Psoriasis. Although there has been interest in using oral Baikal skullcap for psoriasis, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Seizures. Although there has been interest in using oral Baikal skullcap for seizures, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral and intravenous Baikal skullcap for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of Baikal skullcap for this purpose. More evidence is needed to rate Baikal skullcap for these uses.

(Read more about BAIKAL SKULLCAP)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral gardenia for anxiety, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Dementia. Although there has been interest in using oral gardenia for dementia, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Depression. Although there has been interest in using oral gardenia for depression, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Diabetes. Although there has been interest in using oral gardenia for diabetes, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Hypertension. Although there has been interest in using oral gardenia for hypertension, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Influenza. Although there has been interest in using oral gardenia for influenza, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Insomnia. Although there has been interest in using oral gardenia for insomnia, there is insufficient reliable information about the clinical effects of gardenia for this purpose.
• Stroke. Although there has been interest in using oral gardenia for stroke, there is insufficient reliable information about the clinical effects of gardenia for this purpose. More evidence is needed to rate gardenia for these uses.

(Read more about GARDENIA)

POSSIBLY EFFECTIVE

• Bleeding. Intramuscular motherwort injections, alone or in combination with standard treatment such as oxytocin, might reduce volume of blood loss and duration of bleeding after vaginal delivery, caesarian section, or induced abortion. Details: In females with postpartum bleeding after vaginal birth, most research shows that adding motherwort injection to oxytocin or carboprost treatment is more effective than those treatments alone. A meta-analysis of 29 low quality trials shows that injection with motherwort 40-140 mg, in addition to varying doses of oxytocin, is more effective than oxytocin alone for reducing blood loss after vaginal delivery (101890). This combination reduces the mean blood loss within 2 and 24 hours of delivery by 55 mL and 85 mL, respectively. Also, the risk of postpartum hemorrhage, defined as an estimated blood loss of at least 400 mL within 2 hours or at least 500 mL within 24 hours, is reduced by 71%, based on meta-analysis of 18 trials. Meta-analysis of 8 trials also shows motherwort alone to be more effective than oxytocin for reducing blood loss within 24 hours of delivery, but not within 2 hours of delivery. Meta-analysis of 4 trials shows that motherwort 40-200 mg is as effective as oxytocin for reducing the risk of postpartum hemorrhage (101890). Studies were all very low to low quality, with moderate to high risk of bias, and conducted in China, the latter of which limits generalizability to other geographic regions. In females with post-caesarian bleeding, adding motherwort injection to oxytocin reduces blood loss and the rate of post-partum hemorrhage when compared with using oxytocin alone. In a large clinical trial, motherwort 40 mg was injected into the uterus during the caesarian section, followed by 20 mg intramuscular injections every 12 hours over the next 36 hours. However, motherwort injection into the uterus does not seem to be more effective than oxytocin for reducing bleeding during the caesarian section (94203). However, a meta-analysis of 8 trials shows that prophylactic injection with motherwort 60-200 mg, in addition to carboprost 250 mcg, reduces the mean blood loss within 2 and 24 hours of delivery by 127 mL and 147 mL, respectively, with a 72% decrease in the incidence of postpartum hemorrhage over carboprost alone (101891). In 7 of the 8 trials the mode of delivery was caesarian section and 1 was a vaginal delivery. A large observational study suggests that intramuscular injection of motherwort into the uterus combined with intravenous oxytocin is associated with a lower risk of post-partum hemorrhage after caesarian section when compared with intravenous oxytocin plus intramuscular injection of oxytocin into the uterus (112291). A meta-analysis of 9 clinical trials among patients undergoing induced abortion shows that motherwort injection combined with oxytocin lowers the volume of blood loss both 2 hours and 24 hours after the procedure when compared with oxytocin alone (112292). However, motherwort alone is not more effective than oxytocin for blood loss post-abortion. Meta-analysis indicates that motherwort injected alone or with oxytocin reduces the duration of blood loss compared with oxytocin or no treatment. Studies were primarily of very low quality, and all studies were conducted in China, limiting generalizability to other populations and geographic locations.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Oral motherwort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in males experiencing alcohol withdrawal syndrome with disordered sleep, anxiety, and irritability shows that a single dose of a combination product containing motherwort 50 mg, valerian 170 mg, hops 50 mg, and lemon balm 50 mg, taken 1 hour before bedtime, improves sleep quality and decreases awakenings when compared with placebo (63884).
• Amenorrhea. Although there has been interest in using oral motherwort for amenorrhea, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Anxiety. It is unclear if oral motherwort is beneficial in patients with anxiety. Details: Preliminary clinical research in adults with anxiety and hypertension shows that taking a specific preparation of motherwort extracted in soybean oil (Farmagen Ltd.) 600 mg orally twice daily for 28 days reduces anxiety and depression scores when compared with baseline. A significant improvement occurred in 32% of subjects, and a moderate improvement occurred in 48% of subjects (94209). The validity of this finding is limited by the lack of a comparator group.
• Arrhythmia. Although there has been interest in using oral motherwort for arrhythmia, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Asthma. Although there has been interest in using oral motherwort for asthma, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Cancer. Although there has been interest in using oral motherwort for cancer, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Dysmenorrhea. Although there has been interest in using oral motherwort for dysmenorrhea, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Flatulence. Although there has been interest in using oral motherwort for flatulence, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Heart failure. Although there has been interest in using oral motherwort for heart failure, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Herpes zoster (shingles). Although there has been interest in using topical motherwort for herpes zoster, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Hypertension. It is unclear if oral motherwort is beneficial in patients with hypertension. Details: Preliminary clinical research in adults with hypertension and anxiety shows that taking a specific preparation of motherwort extracted in soybean oil (Farmagen Ltd.) 600 mg orally twice daily for 28 days reduces blood pressure when compared with baseline. In subjects with mild hypertension, systolic and diastolic blood pressure decreased by 10% and 11%, respectively. In subjects with more severe hypertension, systolic and diastolic blood pressure decreased by 7% and 11%, respectively (94209). The validity of this finding is limited by the lack of a comparator group.
• Hyperthyroidism. Although there has been interest in using oral motherwort for hyperthyroidism, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Insomnia. Although there has been interest in using oral motherwort for insomnia, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Menopausal symptoms. Oral motherwort has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with menopause shows that taking a combination of motherwort, burdock, dong quai, licorice root, and wild yam three times daily for 12 weeks reduces the number and severity of menopausal symptoms, such as hot flashes, sleep problems, mood changes, and vaginal dryness, in 71% of patients, compared with 17% of patients taking a placebo (48522).
• Pruritus. Although there has been interest in using topical motherwort for pruritus, there is insufficient reliable information about the clinical effects of motherwort for this purpose.
• Wound healing. Although there has been interest in using topical motherwort for wound healing, there is insufficient reliable information about the clinical effects of motherwort for this purpose. More evidence is needed to rate motherwort for these uses.

(Read more about MOTHERWORT)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there is interest in using oral poria mushroom for cancer, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral poria mushroom for CFS, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Chronic kidney disease (CKD). Although there is interest in using oral poria mushroom for CKD, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral poria mushroom for COVID-19, there is insufficient reliable information about the clinical effects of poria mushroom for this purpose.
• Dementia. Although there is interest in using oral poria mushroom for dementia, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Diabetes. Oral poria mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of generally small clinical trials in patients with type 2 diabetes shows that taking Chinese herbal medicine combinations containing poria mushroom for 2-24 weeks along with hypoglycemic medications modestly reduces fasting blood glucose and glycated hemoglobin levels when compared with control groups taking hypoglycemic agents only. There were also modest improvements in levels of triglycerides and low-density lipoprotein (LDL) cholesterol and in insulin sensitivity (111920). Given the large number of other ingredients in the available formulations, it is unclear if any beneficial effects are related to poria mushroom, other ingredients in the formulation, or their combination.
• Diarrhea. Although there is interest in using oral poria mushroom for diarrhea, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Endometriosis. Although there is interest in using oral poria mushroom for endometriosis, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Influenza. Oral poria mushroom has only been evaluated for influenza vaccine enhancement in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking a product containing poria mushroom extract, rosemary extract, and aloe gel powder twice daily for 28 days prior to and following an influenza vaccination does not affect upper respiratory tract illness symptoms, severity, duration, or medication-related use when compared with taking placebo (111921). It is unclear if this study was large enough to detect differences between groups. Also, the effect of poria mushroom itself on influenza vaccine enhancement is unclear.
• Tinnitus. Although there is interest in using oral poria mushroom for tinnitus, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Urinary tract infections (UTIs). Although there is interest in using oral poria mushroom for UTIs, there is insufficient reliable information about the clinical effects of poria mushroom for this use. More evidence is needed to rate poria mushroom for these uses.

(Read more about PORIA MUSHROOM)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Oral Baikal skullcap 0.5-3.52 grams daily has been used with apparent safety for up to 8 weeks (92776,101738,101739,110023). However, a high quality assessment of safety has not been conducted. A specific product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been associated with an increased risk for liver and lung injury. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination. There is insufficient reliable information available about the safety of Baikal skullcap when used intravenously or topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about BAIKAL SKULLCAP)

There is insufficient reliable information available about the safety of gardenia.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about GARDENIA)

POSSIBLY SAFE ...when used orally and appropriately. A motherwort extract in soybean oil has been used with apparent safety at doses of 1200 mg daily for up to 28 days (94209) ...when administered intramuscularly, short-term. One or more intramuscular injections have been used with apparent safety in total combined doses of 40-200 mg over 48 hours or less to prevent and/or stop postpartum bleeding (94203,101890,101891,101892). Post-marketing surveillance of over 8000 females found that a specific motherwort product (Chengdu No 1 Pharma Company Ltd) has been used without significant adverse effects for a duration of 48 hours or less (104855) ...when administered by intrauterine injection, short-term. Post-marketing surveillance of over 1800 patients found that a specific motherwort product (Chengdu No 1 Pharma Company Ltd) has been used without significant adverse effects for a duration of 48 hours or less (104855).

PREGNANCY: LIKELY UNSAFE
when used orally or by injection. Alkaloids present in motherwort have uterine stimulant effects (4,12,19).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about MOTHERWORT)

There is insufficient reliable information available about the safety of poria mushroom.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about PORIA MUSHROOM)

ALCOHOL (Ethanol) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.  Details Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily (33075). It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.  Details Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro (6292). Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin (33408). However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT) (101738). Until more is known, use cautiously.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.  Details Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure (33374).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.  Details In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) (101736). The clinical significance of this effect is unclear.

CNS DEPRESSANTS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.  Details In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties (6290,6291,33477). Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.  Details In vitro evidence suggests that constituents of Baikal skullcap inhibit the activity of CYP1A2 (33346,33484). This effect has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.  Details In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes (33484). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.  Details In vitro evidence suggests that Baikal skullcap has estrogenic activity (16061).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.  Details Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion (5541). The dose of lithium might need to be decreased.

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.  Details Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual (16395). Baikal skullcap might also affect other OATP1B1 substrates (16396,16397,16398).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.  Details In vitro and animal research suggests that baicalein, oroxylin A, and wogonin, constituents of Baikal skullcap, can inhibit P-glycoprotein (33372,33395,33440,33462). This effect has not been reported in humans.

(Read more about BAIKAL SKULLCAP)

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, gardenia might increase the effects and adverse effects of stimulant laxatives.  Details Animal research shows that geniposide, a glucoside found in gardenia fruit, may function as a laxative and cause diarrhea when taken orally (26534).

(Read more about GARDENIA)

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking motherwort concomitantly with other CNS depressants may increase the risk of sedation.  Details Motherwort has been reported to cause CNS depression and sedation (19,94205).

(Read more about MOTHERWORT)

ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, poria mushroom might decrease the clinical effects of anticholinergic drugs.  Details In animal research, poria mushroom essential oil reduces acetylcholinesterase activity (111917). This interaction has not been shown in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, poria mushroom might have additive effects when used with cholinergic drugs.  Details In animal research, poria mushroom essential oil reduces acetylcholinesterase activity (111917). This interaction has not been shown in humans.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking poria mushroom extract may enhance the therapeutic and adverse effects of sedatives.  Details Animal research shows that poria mushroom extract has sedative properties (111916). This interaction has not been shown in humans.

(Read more about PORIA MUSHROOM)

General ...Orally, Baikal skullcap seems to be well-tolerated. There is currently a limited amount of information on the adverse effects of intravenous and topical Baikal skullcap.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, erythema, nausea, pruritus, and vomiting.
Intravenously: Skin reactions.
Topically: Dermatitis.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity and hypersensitivity pneumonitis have been reported with a specific combination product (Limbrel, Primus Pharmaceuticals) containing extracts of Baikal skullcap and catechu.

Cardiovascular ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, elevated triglyceride levels occurred in 1 of 10 patients who received 400 mg every 8 hours and 2 of 10 patients treated with 600 mg every 8 hours, compared with 0 of 10 patients who received 200 mg every 8 hours and 0 of 6 patients who received placebo. Triglyceride elevations were considered mild and resolved after discontinuation (110023).

Dermatologic ...Orally, taking Baikal skullcap may cause erythema and pruritus (105867). Intravenously, Baikal skullcap as part of a Tanreqing injection has been associated with reports of skin reactions in some pediatric patients (96281).
Topically, several cases of allergic contact dermatitis have been reported after applying sunscreen containing Baikal skullcap extract (105869,105870). Allergic contact dermatitis has also been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing Baikal skullcap root extract 0.5% and resveratrol 1%. Patch testing identified a positive reaction to both ingredients (110024). Baikal skullcap-induced dermatitis appears to respond to treatment with a topical corticosteroid and calcineurin inhibitor (105870).

Gastrointestinal ...Orally, use of Baikal skullcap has been associated with epigastric pain, abdominal pain, constipation, diarrhea, nausea, and vomiting (101738,105867).

Hepatic ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of acute liver damage. There have been at least five published reports of liver damage associated with this product. In all cases, the patients were females aged 54-68 years taking doses of 250-500 mg twice daily for 1-3 months. Signs and symptoms included jaundice, pruritus, abdominal pain, fever, rash, and elevated serum bilirubin and liver transaminase levels. All patients fully recovered and levels normalized within 3 months after discontinuation (18009,96282). In addition to these published case reports, approximately 30 liver-related adverse events have been reported to the manufacturer of this product (18009). The mechanism of hepatotoxicity is unclear (18009,18010); it is estimated that the incidence of hepatotoxicity with this product is around 1 in 10,000, although the actual incidence is unknown (18010). In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.
Hepatotoxicity has also been reported in two patients taking a specific dietary supplement (Move Free Advanced, Reckitt Benckiser) containing Baikal skullcap, black catechu, glucosamine, chondroitin, and hyaluronic acid (33460) and in a patient taking Baikal skullcap, elderflower, horseradish, and white willow (101737). The investigators determined that the hepatotoxicity was likely caused by Baikal skullcap in these cases (33460,101737). Additionally, cases of liver injury are reported in 4 of 37 patients taking various Kampo formulations containing Baikal skullcap and other herbs daily. Patients presented with elevated liver function tests 7 to 38 days after consumption (112179). It is unclear if this adverse effect is from Baikal skullcap, other ingredients, or the combination.
In a small study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, liver transaminase elevations occurred in 2 of 10 patients who received 400 mg every 8 hours for 6 days, compared with 0 of 6 patients who received placebo. No patients receiving either 200 mg or 600 mg every 8 hours experienced liver transaminase elevations. The elevations were considered mild and resolved after discontinuation (110023).

Pulmonary/Respiratory ...A specific combination product (Limbrel, Primus Pharmaceuticals) containing flavocoxid, a mixture of Baikal skullcap flavonoid extract and catechu extract, has been linked to several reports of hypersensitivity pneumonitis. Symptoms include fever, chills, headache, cough, chronic bronchitis, shortness of breath, weight loss, and fatigue. In 2017, the US Food and Drug Administration (FDA) formally requested the recall of all non-expired lots of this product due to the risk for liver and lung injury (106042). It is unclear if these effects were due to Baikal skullcap, catechu, or the combination.

Renal ...Orally, in a small clinical study evaluating the safety of baicalein, a constituent of Baikal skullcap, in healthy adults, proteinuria of undefined severity occurred in 1 of 10 patients who received 200 mg every 8 hours for 6 days, 3 of 10 patients who received 400 mg every 8 hours for 6 days, and 5 of 10 patients who received 600 mg every 8 hours for 6 days, compared with 1 of 6 patients who received placebo. The proteinuria was considered mild and resolved after discontinuation (110023).

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General ...There is currently a limited amount of information on the adverse effects of gardenia.
Most Common Adverse Effects:
Topically: Allergic contact dermatitis in sensitive individuals.

Dermatologic ...Topically, exposure to gardenia fruit extract or the whole plant has been associated with allergic contact dermatitis (26518,49078).
Orally, there is a case report of blue-gray skin pigmentation associated with taking a product containing the extracts of gardenia fruit, phellodendron bark, and licorice for 7 years in a 77-year-old female. The pigmentation was thought to be due to melanin deposition enhanced by genipin, a constituent of gardenia. The patient gradually improved over 9 months after stopping this treatment (102698).

Gastrointestinal ...Orally, there are case reports of mesenteric phlebosclerosis, a thickening of the walls of the intestine and mesenteric veins, which can lead to obstruction and occlusion. Typical presenting symptoms are paroxysmal abdominal pain with nausea and vomiting, and imaging studies reveal thickening and stiffening of the walls of the ascending and transverse colon, with dark purple discoloration of the colonic and rectal mucosa, and linear calcification of the mesenteric veins. Treatment is supportive and conservative, leading to a slow resolution of signs and symptoms. In one case a 61-year-old female had been taking a Chinese herbal combination containing extracts of gardenia fruit, Baikal skullcap root, goldthread, phellodendron bark, honeysuckle, rhubarb, anemarrhenae, and trichosanthis root for 8 years (112954). In another case, a 77-year-old female took a product containing extracts of gardenia fruit, phellodendron bark, and licorice for 7 years. Mesenteric phlebosclerosis is thought to be caused by genipin, formed from geniposide after hydrolysis by intestinal bacteria. It is absorbed from the intestine, reacting with proteins in mesenteric veins, leading to progressive fibrosis, calcification, and venous occlusion (102698,112954).

Immunologic ...Topically, exposure to gardenia fruit extract or the whole plant has been associated with allergic contact dermatitis (26518,49078).

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General ...Orally or via intramuscular or intrauterine injection, motherwort appears to be generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, stomach irritation.
Topically: Contact dermatitis, photosensitivity.
Intramuscular / Intrauterine: Abdominal pain, erythema, eyelid edema, fever, nausea, pruritus, rash.

Dermatologic ...Motherwort leaves can cause contact dermatitis, and the oil may cause photosensitivity reactions (4). Intramuscularly and via intrauterine injection, mild erythema, rash, and pruritus have been reported (101892,104855).

Gastrointestinal ...Orally, use of motherwort in amounts greater than 3 grams can cause diarrhea and stomach irritation (12). Intramuscularly and via intrauterine injection, abdominal pain and nausea have been reported (104855).

Genitourinary ...Orally, use of motherwort in amounts greater than 3 grams can cause uterine bleeding (12).

Immunologic ...Motherwort can also cause allergic reactions in sensitive individuals (4). Intramuscularly and via intrauterine injection, transient fever and chills lasting less than 24 hours have been reported (104855).

Ocular/Otic ...Intramuscularly and via intrauterine injection, transient eyelid edema lasting less than 24 hours has been reported (104855).

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General ...Orally, poria mushroom seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.

Immunologic ...Allergic reactions have been reported rarely, including allergic rhinitis and allergic asthma (12).

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