Wulinshen

Wulinshen (Xylaria nigripes): A Comprehensive Reference

Nomenclature and Taxonomic Identity

The name Wulinshen (also rendered as Wu Ling Shen, Wulingshen, or Wu-Ling-Shen) most commonly refers to the medicinal fungus Xylaria nigripes (Kl.) Sacc. in the contemporary scientific and clinical literature. Xylaria is a genus of ascomycetous fungi in the family Xylariaceae. Xylaria nigripes is a rare medicinal fungus known as Wulingshen in China; commonly known also as Leizhenzi, it possesses warm properties and a slightly bitter taste, and has been utilized in Chinese medicine for over 2,000 years.

It is important to note that the term "Wulinshen" can cause taxonomic confusion in supplement contexts. Some sources use "Wulinshen" to refer instead to Bombyx batryticatus, the stiff silkworm — a traditional ingredient derived from silkworm larvae infected by the fungus Beauveria bassiana. These are two entirely distinct biological entities. In the peer-reviewed pharmacological and clinical literature, as well as in approved Chinese pharmaceutical preparations, Wulinshen most definitively refers to Xylaria nigripes, and that identification is the primary focus of this article. The second entity, Bombyx batryticatus (also called Jiangcan), is addressed separately below under "Nomenclature Note."

Source and Natural Ecology

Wulinshen (Xylaria nigripes) is a fungus found underground, several feet below the surface, inside the nests of the Odontotermes formosanus termite, where it grows as a compact, filamentous mass. It serves as a primary source of food for these termites. Certain Xylaria species form massive sclerotia of several centimeters in diameter within underground nests of macrotermitine termites; vernacularly, these sclerotia are called Wulingshen in China or Nilamanga and Puttumanga in southern India. Xylaria nigripes was once commonly regarded as the sole producer of such massive sclerotia, though they are in fact produced by at least six Xylaria species, including X. nigripes and its close relatives.

Xylaria sclerotia have been used in folk medicine for treating a wide range of ailments, whereas dried mycelia from cultures are used mainly for soothing anxiety, depression, insomnia, and some neurological disorders.

Because wild Xylaria nigripes is very rare, difficult to find, and extremely expensive, researchers have developed a patented fermentation process that allows for the production of a pure proprietary extract. Wuling powder, a fermented form of X. nigripes, leverages biotechnology to harness the fungus's health benefits, showing significant therapeutic efficacy clinically.

Traditional and Historical Use

Known as Wulingshen or Leizhenzi, the fungus has been utilized in Chinese medicine for over 2,000 years. Its pseudo-root extending from the petiole base to the subterranean sclerotia is used medicinally to enhance brain function, reduce dampness, soothe nerves, clear collaterals, stimulate blood circulation, and boost immunity. Traditionally, X. nigripes has been employed to treat conditions such as postpartum hemorrhage, hypogalactia, hernia, palpitations, insomnia, and infantile convulsions.

Xylaria nigripes is a rare medicinal fungus known as Wulingshen in China. It has a neutral and sweet nature and belongs to the heart and kidney meridians in Traditional Chinese Medicine (TCM). Rich in a variety of bioactive ingredients, it serves as a nutrient-dense food and a therapeutic agent for disease prevention.

In folk medicine, X. nigripes is used to treat central nervous system-associated disorders such as insomnia, anxiety, depression, and spatial memory impairment. In Chinese medicine, X. nigripes is used in crude form to cure several human ailments such as insomnia and trauma. It also serves as a nerve tonic, sedative, diuretic, and for reduction of convulsions in infants, and to discontinue heart palpitations. It also promotes lactation and prevents loss of blood in nose and lungs following childbirth.

Wuling capsule, made from mycelia of precious Xylaria nigripes, was approved in 1999 by the China State Food and Drug Administration (Authorized Document Number: Z19990048 in Chinese medicine) for the treatment of neurasthenia (insomnia, amnesia, neurosis, vertigo, exhaustion syndrome), depression, anemia, women's menstrual disorder, and diseases during climacterium in men and women.

Nomenclature Note: Bombyx batryticatus ("Jiangcan")

As noted, some English-language supplement sources apply "Wulinshen" to Bombyx batryticatus, a distinct traditional Chinese medicinal substance. Bombyx batryticatus is the dried larva of Bombyx mori L. (silkworm of 4–5 instars) that has been infected by Beauveria bassiana; it is called Jiangcan in Chinese vernacular and has been used in China for thousands of years. It is also widely used in Korea and Japan.

In traditional medical applications in China, South Korea, and Japan, B. batryticatus has the functions of relieving spasm by calming endogenous wind, dispelling pathogenic wind for relieving pain, dissipating phlegm, and resolving masses. It is used to treat liver wind with phlegm, convulsion, acute panic in children, tetanus, stroke, fever, headache, sore throat, itchy rubella, as well as mumps.

Because the two substances are biologically unrelated and have distinct pharmacological profiles and evidence bases, all references to "Wulinshen" in the clinical literature are parsed carefully throughout this article to indicate which organism is being discussed.

Key Chemical Constituents

Xylaria nigripes (Wulingshen)

The chemical composition of X. nigripes is exceptionally diverse, encompassing alkaloids, sterols, chromogenic ketones, terpenoids, isocoumarin derivatives, resorcinol derivatives, naphthalenone derivatives, and other miscellaneous compounds. Additionally, polysaccharides constitute a major component in the chemical composition of X. nigripes, particularly in its crude form.

In vivo and in vitro studies have attributed the bioactivities of X. nigripes to chemical compounds including intracellular and extracellular polysaccharides, adenosine, total polyphenols, and triterpenoids in mycelia. Under optimized submerged fermentation conditions, production of bioactive ingredients such as extracellular polysaccharides (2.36 ± 0.18 mg/mL), intracellular polysaccharides (2.38 ± 0.07 mg/g), adenosine (43.27 ± 2.37 mg/g), total polyphenols (36.57 ± 1.36 mg/g), and triterpenoids (31.29 ± 1.17 mg/g) has been documented in a shake flask culture.

Of particular pharmacological interest are the amino acid neurotransmitter precursors. Wulinshen contains glutamic acid, gamma-aminobutyric acid (GABA), and glutamate decarboxylase, all of which are known to assist in the uptake of GABA by specific brain cell receptors that exert a mild tranquilizing effect on the central nervous system.

The polysaccharides of X. nigripes have also been characterized for their immune-modulatory and anti-inflammatory potential. Studies of water-soluble non-digestible polysaccharides from fruiting bodies of cultivated X. nigripes strains showed that one variant (TXNP) had a triple helix conformation and molecular weight of 853.8 kDa, while another (CXNP) had a molecular weight of 14.7 kDa; the monosaccharide composition of TXNP was predominantly glucose, whereas CXNP contained xylose, mannose, and glucose.

Bombyx batryticatus (Jiangcan — where "Wulinshen" is applied to this substance)

Many studies indicate B. batryticatus contains various compounds, including proteins and peptides, fatty acids, flavonoids, nucleosides, steroids, coumarin, polysaccharides, and others. Key identified flavonoids include quercetin and kaempferol, which have been quantified by RP-HPLC. A notable bioactive alkaloid is 1-deoxynojirimycin (1-DNJ), a potent alpha-glucosidase inhibitor. Research identified quercetin-7-O-β-d-4-O-methylglucoside as a characteristic compound of the stiff stage of B. batryticatus, its relative abundance increasing with stiff time, making it a candidate index component for quality control.

A 2022 anticonvulsant study identified additional bioactive compounds: the chloroform extract fractions of B. batryticatus showed a significant anticonvulsant effect, and 17 compounds were identified including lumichrome, pheophorbide A, and episyringaresinol 4′-O-beta-d-glucopyranose that were found for the first time.

Mechanisms of Action

GABAergic and Neurotransmitter Modulation (X. nigripes)

The most extensively investigated mechanism for X. nigripes involves the GABAergic neurotransmitter system. One essential compound the body requires for sleep initiation is gamma-aminobutyric acid (GABA), which allows the brain to communicate important inhibitory messages throughout the body. GABA acts as a neurotransmitter in the brain, promoting relaxation; GABA-T breaks down GABA into SSA and glutamate. Glutamate decarboxylase (GAD) is an enzyme that plays a critical role in the balance of neurotransmitters in the brain, specifically GABA.

A study published in the Journal of Biochemistry and Biotechnology examined the effects of three different botanical compositions — Xylaria nigripes extract (XE), X. nigripes + Panax notoginseng extract (XPE), and X. nigripes + Panax notoginseng + Cuscuta chinensis extract (XPCE) — on GABA content, GABA transaminase (GABA-T), glutamate decarboxylase (GAD), cell viability, and amyloid-β protein aggregation levels in PC12 neuron cells. All three compositions could effectively improve GABA production and also increase the activity of glutamate GAD along with decreased GABA-T activity in PC12 cells in a dose-dependent fashion.

Neuroprotection and Antioxidant Activity (X. nigripes)

In a study elucidating mechanisms of neuroprotective effects, X. nigripes mycelia were produced by fermentation. Hot water extract and 70% ethanol extract of X. nigripes mycelia were evaluated on hydrogen peroxide (H₂O₂)-induced apoptosis in PC12, a rat pheochromocytoma cell line. Extracts of X. nigripes, along with its components and secondary metabolites, have shown a variety of biological activities, such as neuroprotection, anti-inflammatory effects, antioxidant capabilities, and acetylcholinesterase inhibitory action.

Anti-inflammatory Pathways — Polysaccharides (X. nigripes)

Both TXNP and CXNP polysaccharide fractions of X. nigripes dose-dependently suppressed the production of NO, IL-1β, TNF-α, and PGE2, as well as the expression of iNOS, COX-2, and NF-κB in lipopolysaccharide-induced RAW264.7 macrophages.

Anticonvulsant Mechanisms (B. batryticatus)

Bombyx batryticatus is an anticonvulsant animal medicine in TCM and acts on the central nervous system. Pentylenetetrazol, a GABAA receptor antagonist, is commonly used as a convulsing drug in experimental studies of B. batryticatus, implying a GABAergic mechanism of anticonvulsant action.

Alpha-Glucosidase Inhibition and Hypoglycemic Effects (B. batryticatus)

The compound 1-deoxynojirimycin (1-DNJ), present in B. batryticatus, inhibits alpha-glucosidase, an intestinal enzyme that cleaves complex carbohydrates into glucose. Extracts of B. batryticatus exhibit strong inhibitory activity against α-glucosidase; the highest levels of 1-DNJ, flavonoids, phenolics, and other compounds were found in Thai silkworm races on the 3rd day of the fifth instar, with an IC50 value of 2 mg (silkworm powder)/mL for α-glucosidase.

Scientific Evidence by Area of Use

1. Insomnia and Sleep Quality (X. nigripes / Wuling Capsule)

This is the area for which the strongest human clinical evidence exists. Wuling capsule is a single herbal formula derived from Xylaria nigripes mycelia and has been applied in clinical treatment of insomnia disorder for decades in China, but the results of its therapeutic efficacy in studies were inconsistent.

Key RCT (2013): A multicenter, randomized, double-blind, placebo-controlled study was conducted with Wuling Capsule, a single herbal formula from mycelia of precious Xylaria nigripes (Kl.) Sacc., whose pharmacological function is a tranquilizing effect on the central nervous system. The participants received either placebo (n=92) or Wuling capsule (n=94) for 4 weeks and a follow-up period of 2 weeks. Compared between pre-treatment and post-treatment, the global Pittsburgh Sleep Quality Index (PSQI) scores in both the Wuling capsule group and placebo group improved significantly (P<0.01). However, there was no significant difference between the Wuling capsule group and the placebo group (P>0.05). This result indicates both groups improved but the active treatment did not outperform placebo on the primary sleep outcome in this trial.

2022 Systematic Review and Meta-analysis: Wuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder. However, these findings require careful recommendation due to the high heterogeneity and high risk of bias in the included trials. The review was published in Sleep Medicine (2022 May; 93:1–14). Critically, the senior author of this meta-analysis concluded: "The findings of this study are not strong enough to support the use of Wuling capsule as a treatment for insomnia disorder."

Retrospective clinical study: A study comparing 60 patients treated with Wuling capsule (research group) against 54 patients treated with estazolam (control group) evaluated clinical efficacy, adverse reactions, PSQI scores, fatigue state, and negative emotions. After treatment, the research group exhibited notably lower PSQI scores, and lower physical and mental fatigue scores than the control group. After treatment, the research group also demonstrated evidently lower anxiety and depression scores than the control group.

Evidence assessment: Human clinical evidence for insomnia exists in the form of RCTs, but the pivotal multicenter RCT failed to demonstrate superiority over placebo on the primary outcome, and the 2022 meta-analysis of RCTs — while showing overall positive signal — was limited by high heterogeneity and high risk of bias. Evidence is currently insufficient to make firm efficacy claims for insomnia.

2. Major Depressive Disorder (X. nigripes / Wuling Capsule)

In China, Wuling capsule, a traditional Chinese medicine consisting of Wuling mycelia of Xylaria nigripes (Kl.) Sacc. (a rare type of fungus), is used to treat major depressive disorders.

2016 Meta-analysis: A meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of Wuling capsule alone with Wuling capsule–antidepressant combination in the treatment of major depressive disorders. Two assessors independently selected studies, extracted data, and conducted quality assessment and data synthesis. Standard mean difference, risk ratio (RR) ± 95% CI, the number needed to treat, and the number needed to harm were analyzed. A total of 12 randomized controlled trials (880 patients; mean age ± standard deviation, 39.7 ± 12.5 years; male patients, 41%) were identified, including 4 trials with Wuling capsule alone (n = 340) and 8 with Wuling capsule–antidepressant (sertraline, mianserin, mirtazapine, and paroxetine) combination.

Epilepsy-related depression (2015 RCT): In a randomized, double-blind, placebo-controlled study done on 104 patients with epilepsy, subjects either received Xylaria extract or a placebo over 12 weeks. The results showed that Xylaria was effective at alleviating depressive symptoms when compared to placebo.

Post-stroke depression: Wuling capsule was effective in treating post-stroke and other comorbid depression both in clinical and basic research.

Evidence assessment: Multiple RCTs and at least one meta-analysis have examined Wuling capsule for depression. Evidence is more consistent here than for insomnia but is again based primarily on China-based trials with variable methodological quality. Independent replication in larger, more rigorously blinded trials is lacking.

3. Anxiety and Mood Support (X. nigripes)

Wuling capsule, composed of Wuling mycelia powder made by fermenting and processing Xylaria nigripes (Kl.) Sacc., is clinically commonly used to alleviate depression and anxiety. Animal models have demonstrated anxiolytic properties, and the GABAergic mechanism outlined above provides a plausible biological rationale. However, dedicated placebo-controlled trials focused exclusively on anxiety as a primary outcome are limited in number and scope in the peer-reviewed literature available outside China.

4. Neuroprotection and Memory (X. nigripes)

In vivo and in vitro studies have demonstrated bioactivities of X. nigripes including prevention of spatial memory impairment and neuroprotective activities. Xylaria has been shown in rats to help against spatial memory impairment induced by sleep deprivation.

Evidence assessment: Memory-related evidence for X. nigripes remains at the level of animal studies (in vivo) and cell culture (in vitro). No adequately powered human clinical trials focusing on cognitive outcomes have been identified in the available peer-reviewed literature.

5. Anticonvulsant Activity (B. batryticatus)

Where "Wulinshen" is applied to Bombyx batryticatus, the anticonvulsant application is the most historically prominent. The anticonvulsant activity of B. batryticatus is very remarkable; quality control and quality formation studies have focused on this anticonvulsant activity as the primary pharmacological benchmark.

The anticonvulsant effects of B. batryticatus with a stiff time of one, five, and nine days (D1, D5, and D9, respectively) and healthy silkworm of the same developmental stage (SW) were determined by animal experiment. The dynamic changes in chemical composition were analyzed using UPLC-Q-TOF-MS-based metabolomics. D5 and D9 B. batryticatus exhibited significant anticonvulsant effects (p<0.05 and p<0.01, respectively). Accordingly, principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) indicated that the chemical composition of D5 and D9 B. batryticatus changed significantly.

Evidence assessment: Anticonvulsant evidence for B. batryticatus is based on animal experiments (rodent convulsion models) and in vitro studies. No controlled human clinical trials of B. batryticatus specifically for epilepsy were identified in the available peer-reviewed sources.

6. Glycemic Control — Hypoglycemic Effects (B. batryticatus)

Modern pharmacological investigations have proved that water or alcohol extracts of B. batryticatus have anticonvulsant, antiepileptic, anticoagulant, hypoglycemic, antioxidant, and antitumor activities. The hypoglycemic mechanism is linked to 1-DNJ's alpha-glucosidase inhibitory activity. The total reducing power, hydroxyl radical scavenging and superoxide anion radical scavenging activities, as well as α-glucosidase inhibitory activity of Bombyx batryticatus extract were superior to those of normal silkworm larvae extract; the IC50 value of Bombyx batryticatus extract for α-glucosidase was 5.76 mg/mL, while that of normal silkworm larvae extract was 7.0 mg/mL.

Evidence assessment: Hypoglycemic evidence for B. batryticatus is primarily from animal models (diabetic rodents) and enzymatic assays. Human clinical data are not available in the reviewed sources.

7. Antitumor and Anticancer Activity (B. batryticatus)

B. batryticatus possesses significant anti-proliferative effects on human cancer cell lines, such as cervical cancer, liver cancer, and gastric cancer. Ethanol extracts of B. batryticatus possessed significant anti-cervical cancer effect against HeLa cells at concentrations of 3.0–11.0 mg/mL, and the anticancer mechanism may be associated with induction of apoptosis by downregulating expression of Bcl-2. Flavonoids isolated from B. batryticatus (50.0–500.0 µg/mL) also showed strong anti-cervical cancer activities through suppressing proliferation of HeLa cells in a concentration-dependent manner.

Evidence assessment: All anticancer findings for B. batryticatus are from in vitro cell-line studies. No human clinical evidence exists, and these results cannot be extrapolated to clinical benefit.

8. Hepatoprotection (X. nigripes)

Protective effects of Wu-Ling-Shen (Xylaria nigripes) on carbon tetrachloride-induced hepatotoxicity have been reported in mice. This activity is attributed in part to the polysaccharide and polyphenol content of the fungus. Evidence is preclinical (animal model only).

9. Neuroprotection Against Amyloid-beta (B. batryticatus)

Water extracts of Bombyx batryticatus (Bombycis corpus) were examined for protective effect against amyloid-beta (Aβ) 25–35 peptide-induced cytotoxicity; Aβ 25–35-induced cell death was protected by application of the water extract in a dose-dependent manner, and concentrations of 10⁻⁶ to 10⁻⁷ g/mL showed a significant effect compared to exposure to Aβ 25–35 alone. A further study found that Bombycis corpus extract (BCE) can prevent or reduce the neurotoxic actions in the hippocampus of the glutamate agonists NMDA in vitro or AMPA and kainic acid in vitro. These are in vitro findings only.

Body Systems and Health Areas

• Central Nervous System: Extracts from B. batryticatus exert a wide spectrum of pharmacological effects including effects on the nervous system. For X. nigripes, the CNS is the primary target system through GABAergic modulation, sedation, and neuroprotection.
• Sleep: Wuling capsule, composed of Wuling mycelia powder made by fermenting and processing Xylaria nigripes (Kl.) Sacc., is clinically commonly used to alleviate depression and anxiety.
• Mood and Psychiatric: Both RCTs and meta-analyses address depression as a target for Wuling capsule (X. nigripes).
• Metabolic / Glycemic: B. batryticatus is widely used in traditional Chinese medicine for treating convulsions, epilepsy, and hyperglycemia.
• Immune System: Immunomodulatory activity has been demonstrated for X. nigripes in in vivo and in vitro studies.
• Liver: Hepatoprotective activity of X. nigripes has been documented in animal studies.
• Cardiovascular / Hemostasis: Anticoagulant effects of B. batryticatus have been shown both in vivo and in vitro.

Dosage Forms and Reported Dosages

Clinical and Commercial Preparations of Xylaria nigripes

Wuling capsule, the primary pharmaceutical product derived from Xylaria nigripes, is composed of Wuling mycelia powder made by fermenting and processing X. nigripes (Kl.) Sacc. In the pivotal multicenter RCT (2013), the participants received either placebo (n=92) or Wuling capsule (n=94) for 4 weeks, with a follow-up period of 2 weeks. Specific per-dose milligram amounts for the Wuling capsule were not extractable from the available public abstracts reviewed.

For the proprietary extract "Zylaria™" (a formulation of Xylaria nigripes combined with Cuscuta chinensis and Panax notoginseng), commercial product labels report a standardized 500 mg dose per capsule, with directions of 1–3 capsules daily. These are commercially reported figures, not independently replicated in published clinical trials specific to those doses.

For the subchronic toxicity study of a standardized aqueous extract of solid-state cultured X. nigripes, a 90-day subchronic toxicity study was conducted by oral administration of the extract at daily doses of 20, 1,000, and 2,000 mg/kg body weight to Sprague-Dawley rats of both sexes, with the control group given distilled water. These are toxicological study doses used to establish safety margins, not human therapeutic doses.

Preparations of Bombyx batryticatus

In TCM practice, B. batryticatus is traditionally used as a dried whole-body material. In the anticonvulsant rodent studies, crude extracts of B. batryticatus at 20 g/kg were divided into different polarity fractions and administered to groups of mice before injecting pentylenetetrazol (PTZ) to induce convulsions. These are experimental animal doses and do not translate directly to human use. No standardized human clinical dosage for B. batryticatus has been established in the peer-reviewed sources reviewed.

Safety and Toxicology

Xylaria nigripes

The toxicity of X. nigripes had never been systematically evaluated prior to a dedicated safety study; that study aimed to evaluate the safety of a standardized aqueous extract (XNE), an ingredient of commercial products, prepared from solid-state cultured X. nigripes in rats. A 90-day subchronic toxicity study was conducted by oral administration of XNE at daily doses of 20, 1,000, and 2,000 mg/kg body weight to Sprague-Dawley rats of both sexes, with the control group given distilled water. All animals were checked daily for general behavior, body weight changes, and signs of toxicity. At the end of the treatment period, hematological analysis, biochemical analysis, and histopathological examination of organs were conducted.

The clinical trial record for the Wuling capsule insomnia RCT (Lin et al., 2013) included safety monitoring over the 4-week treatment and 2-week follow-up period. In the 2016 meta-analysis of RCTs for major depressive disorder, adverse event data from all 12 included trials were analyzed. The available public abstracts do not provide specific adverse event rates or types beyond the general framing of the safety evaluation.

No studies in the available reviewed sources have specifically identified serious adverse events, drug interactions, or contraindications for X. nigripes at therapeutic doses. Because the compound influences GABAergic signaling, the possibility of additive CNS-depressant effects with other sedative agents is mechanistically plausible, but this has not been characterized in clinical interaction studies identified by this review.

Bombyx batryticatus

The review by Hu et al. (2017) covered not only chemical constituents and pharmacological effects but also toxicity studies of B. batryticatus. Untargeted metabolomic analysis of normal silkworm larvae and Bombyx batryticatus revealed 101 metabolic differences between the two groups, including a significant increase in fatty acids and their derivatives in the Bombyx batryticatus extract. Individuals with silkworm or insect allergies may theoretically be at risk of hypersensitivity reactions, though specific clinical allergy data were not available in the sources reviewed. The compound beauvericin, a cyclic depsipeptide found in B. bassiana-infected material, has been identified as a constituent of B. batryticatus in some chemical characterization studies, and is recognized as a mycotoxin in other contexts; the significance of this in dried, processed medicinal preparations has not been fully characterized in the sources reviewed.

Quality, Standardization, and Regulatory Status

Currently, B. batryticatus is mainly derived from silkworms spontaneously infected by B. bassiana in sericulture. Thus, the supply of B. batryticatus varies each year and the quality is uneven. Due to the lack of efficient production technology and quality control systems, the artificial production of B. batryticatus has not been fully standardized.

For X. nigripes, the development of deep fermentation technology and artificial cultivation of X. nigripes have been successfully achieved, providing more consistent product compared to wild harvesting. Wuling capsule was approved in 1999 by the China State Food and Drug Administration (Authorized Document Number: Z19990048) for the treatment of neurasthenia and depression. It does not hold regulatory approval as a drug in the United States, the European Union, or other Western jurisdictions, where it is marketed as a dietary supplement. The NIH's Dietary Supplement Label Database (DSLD) lists Wulinshen as an ingredient found in US-marketed dietary supplement products.

Current State of Evidence: Summary Assessment

Modern pharmacological studies have verified the important role of X. nigripes in promoting health properties, including antioxidant, sedative-hypnotic, antiepileptic, immune-regulating, and endocrine-regulating activities. Nevertheless, the totality of the published clinical record — particularly for insomnia, the most-studied human endpoint — must be interpreted cautiously. The 2022 meta-analysis concluded that Wuling capsule can safely and effectively improve sleep quality in patients with insomnia disorder, but that these findings require careful recommendation due to high heterogeneity and high risk of bias in the included trials. The strongest human evidence concerns the compound's use as an adjunctive agent alongside antidepressants in major depressive disorder, based on a 2016 meta-analysis of 12 RCTs (880 patients).

For Bombyx batryticatus, numerous investigations have shown that extracts and compounds from B. batryticatus exert a wide spectrum of pharmacological effects both in vivo and in vitro, including effects on the nervous system, anticoagulant effects, antitumor effects, antibacterial and antifungal effects, antioxidant effects, and hypoglycemic effects. However, essentially all of this evidence is preclinical. There is still a need for more comprehensive clinical trials in humans to fully validate the efficacy and safety of Wulinshen as used in modern nutritional products; current evidence is largely preclinical and anecdotal, and standardized preparations and dosages have yet to be established.

References

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• Bombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes. PubMed PMID: 11207060
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