Triterpenes, Beta-Glucans and Hericenones: How Adaptogenic Mushrooms Interact With Stress and Immunity

Adaptogenic mushrooms like Reishi, Lion's Mane, and Chaga interact with stress and immunity through distinct bioactive compounds. Understanding these specific mechanisms, such as Reishi's triterpenes for the HPA axis or Lion's Mane's hericenones for nerve growth, reveals how they modulate bodily balance.

Chloe Bennett

November 9, 2026 · 6 min read

Adaptogenic mushrooms earn their name through chemistry, not folklore. The three most-studied species—Reishi (Ganoderma lucidum), Lion's Mane (Hericium erinaceus) and Chaga (Inonotus obliquus)—each carry distinct bioactive compounds that are understood to act on the body's stress machinery and immune pathways in different ways. Reishi's triterpenes and beta-glucans are proposed to modulate the HPA axis and immune cells directly; Lion's Mane works mainly through hericenones and erinacines that stimulate nerve growth factor; and Chaga's polysaccharides and triterpenes are associated with immune modulation and anti-inflammatory effects. Understanding which compound does what lets you see why these fungi are described as modulators rather than stimulants.

Understanding Adaptogens and the HPA Axis

The hypothalamic-pituitary-adrenal (HPA) axis is your body's central stress response system. When a stressor arrives—physical, emotional, hormonal, even something you ate—the hypothalamus signals the pituitary gland, which prompts the adrenal glands to release hormones such as cortisol. UCLA Health explains that experts believe adaptogens interact with this axis, which initiates the stress response and plays a major role in keeping the body in balance. In other words, the HPA axis is the command center adaptogens are thought to reach.

What makes an adaptogen an adaptogen, rather than just any calming or energizing herb? To qualify, a substance must be nontoxic at normal doses, support the whole body's ability to cope with stress, and help the body return to a stable state. That last criterion is the key one. Adaptogens are understood to work through the endocrine and immune systems to restore balance without overstimulation, as wellness educators at Bask Retreat Center describe it—helping the body regulate itself rather than forcing it in one direction.

This is why practitioners describe adaptogens as modulators. Dr. Michael Ruscio, a functional medicine clinician, notes that adaptogens appear to influence the stress response by supporting the HPA axis, modulating cortisol levels, and reducing oxidative stress and inflammation. In mushrooms specifically, he points to beta-glucans—a type of polysaccharide in fungal cell walls—as playing a major role. The principle holds broadly: adaptogens help the body maintain homeostasis rather than simply revving it up or shutting it down, though specific mechanisms vary by mushroom and compound. And as UCLA Health cautions, what experts know about most adaptogens is still limited.

Reishi Mushroom: Modulating Stress and Immunity

Reishi is one of the oldest medicinal mushrooms in clinical use, and it contains two main groups of active compounds that are proposed to work through distinct mechanisms. According to Dr. Ash of Fishtown Medicine, its triterpenes interact with the HPA axis—the body's main stress command center—to soften the stress response, blunting the sharp edges of cortisol and supporting GABAergic signaling, the calming neural pathway that eases the transition toward sleep. Reishi's beta-glucans, by contrast, act as what he calls "biological scouts" for the immune system.

There is an important evidentiary boundary here. Writing at Triterra Farm, a mushroom cultivator reviewing the human data, is candid that direct human-trial evidence for Reishi alone lowering cortisol is limited: in people, Reishi has been shown to reduce fatigue and improve well-being in a fatigue diagnosis, and to lower anxiety and depression scores as secondary measures in cancer patients and a small student study. The more mechanistic HPA-axis findings come from rodent research, so human evidence for direct cortisol modulation by Reishi on its own is still emerging.

Supporting compounds add context. A randomized trial of a mushroom blend that included Reishi, published in a peer-reviewed journal, reported anti-inflammatory activity and improvements in sleep quality tied to the blend's bioactive compounds. Separately, a study in endurance cyclists notes that Reishi triterpenes have shown antioxidant effects, scavenging free radicals in vitro and enhancing antioxidant enzymes in mice after a month of administration. These findings sketch a plausible stress-and-immunity story, but with varying levels of human evidence behind each piece.

Adaptogenic Mushrooms: Compounds and Mechanisms

The table below consolidates the mapping developed throughout this article—each mushroom, its principal compounds, the system those compounds primarily target, and the proposed mechanism. Use it as a quick reference: whenever you encounter a generalized claim about "adaptogenic mushrooms," check which species and which compounds the claim actually rests on.

Proposed mechanisms of three adaptogenic mushrooms, by compound and target system
Mushroom	Key Bioactive Compounds	Primary Target System	Proposed Mechanism of Action
Reishi (Ganoderma lucidum)	Triterpenes; polysaccharides including beta-glucans	HPA axis and immune system	Triterpenes are understood to interact with the HPA axis to blunt cortisol's sharp edges and support GABAergic signaling that eases the transition to sleep; beta-glucans act on immune cell pathways. Direct human-trial evidence for cortisol modulation by Reishi alone is still emerging.
Lion's Mane (Hericium erinaceus)	Hericenones and erinacines	Nervous system (brain and nerve health)	These compounds promote nerve growth factor synthesis, supporting neurogenesis and neurotransmitter activity; direct evidence for HPA axis or immune modulation is less explicit than for Reishi.
Chaga (Inonotus obliquus)	Polysaccharides and triterpenes	Immune system	Associated with immune modulation and anti-inflammatory responses, which may indirectly support the body's stress response; direct mechanistic links to the HPA axis are not well established.

Proposed mechanisms of three adaptogenic mushrooms, by compound and target system

Mushroom

Key Bioactive Compounds

Primary Target System

Proposed Mechanism of Action

Reishi (Ganoderma lucidum)

Triterpenes; polysaccharides including beta-glucans

HPA axis and immune system

Triterpenes are understood to interact with the HPA axis to blunt cortisol's sharp edges and support GABAergic signaling that eases the transition to sleep; beta-glucans act on immune cell pathways. Direct human-trial evidence for cortisol modulation by Reishi alone is still emerging.

Lion's Mane (Hericium erinaceus)

Hericenones and erinacines

Nervous system (brain and nerve health)

These compounds promote nerve growth factor synthesis, supporting neurogenesis and neurotransmitter activity; direct evidence for HPA axis or immune modulation is less explicit than for Reishi.

Chaga (Inonotus obliquus)

Polysaccharides and triterpenes

Immune system

Associated with immune modulation and anti-inflammatory responses, which may indirectly support the body's stress response; direct mechanistic links to the HPA axis are not well established.

Reading across the rows shows the pattern: all three species are called adaptogenic, but their chemistry points them at different systems. Reishi's dual compound profile—triterpenes aimed at stress hormones, beta-glucans at immune surveillance—makes it the most direct HPA-axis candidate. Lion's Mane's hericenones and erinacines work through nerve growth. Chaga's polysaccharides and triterpenes work through immune and inflammatory pathways. A product marketed for "stress" and one marketed for "immunity" may rely on entirely different mechanisms, which is exactly the distinction the table is designed to surface.