β-Eudesmol, a sesquiterpenoid alcohol, is the main constituent of AL. β-Eudesmol can be also extracted from
Teucrium ramosissimum [
52]. The melting point of β-eudesmol is 72–74 °C. Particularly, β-eudesmol demonstrated a strong inhibitory effect on cancer, and β-eudesmol could protect neuron from inflammatory damage. CCA, or bile duct cancer, which was an uncommon adenocarcinoma that originated from the epithelial cells of bile ducts, is becoming a vital public health problem worldwide. Recent study exerted that β-eudesmol could improve the anti-cancer effect of 5-fluorouracil and doxorubicin in human CCA KKU-100 cells with the high expression of NAD (P) H-quinone oxidoreductase 1 (NQO1). Also, β-eudesmol could inhibit cell growth, migration, NQO1 expression and activity in CCA [
53]. β-Eudesmol showed an inhibitory effect on CCA growth and metastasis in CCA-xenografted nude mouse model according to the results from positron emission tomography-computed tomography (PET-CT). Also, β-eudesmol could prolong the survival time of CCA mice model [
54]. Another study exerted that β-eudesmol could also induce apoptosis, cell cycle arrest at G1 phase, and the cleavage of caspase 3 and caspase 7 in CCA [
55]. Primary liver cancer is the third-leading cause of cancer death all over the world [
56]. Recent studies showed that β-eudesmol isomers could inhibit proliferation of human hepatocellular carcinoma Hep-G2 cells through the induction of apoptosis, according to haematoxylin–eosin and acridine orange ethidium bromide staining results. Further study showed that β-eudesmol could decrease mitochondrial membrane potential and activate caspases [
57]. Recently, β-eudesmol showed the anti-tumor activities in human lung and colon cancer cells. Further study exerted that β-eudesmol (200 μM) significantly decreased A549 cells migration towards type IV collagen (54% inhibition) and fibronectin (60% inhibition). Meanwhile, β-eudesmol (200 μM) also inhibited HT29 cell migration toward type IV collagen and fibronectinline with inhibition of 76% and 63%, respectively [
52]. Abnormal angiogenesis was involved in diverse diseases, such as tumor and diabetic retinopathy. Recently, β-eudesmol showed an inhibitory effect on angiogenesis partly via the arrest of the ERK signaling pathway, suggesting that β-eudesmol could be considered as the drug candidate for treatment of angiogenic diseases. In detail, β-eudesmol had an inhibitory effect on the multiplication of porcine brain microvascular endothelial cells and human umbilical vein endothelial cells (HUVEC). Additionally, β-eudesmol could inhibit the migration of HUVEC, and at the high concentration β-eudesmol could inhibit the ERK1/2 phosphorylation and suppress angiogenesis in subcutaneously implanted Matrigel plugs in mice and in adjuvant-induced granuloma in mice [
58]. Another study showed that β-eudesmol had an inhibitory effect on angiogenesis via inhibiting CREB activation in growth factor signaling pathway, herein demonstrating β-eudesmol as an inhibitory compound of tumor growth. β-Eudesmol at the concentration ranging from 50 to 100 μM had an inhibitory effect on the proliferation of HUVEC stimulated with vascular endothelial growth factor (VEGF, 30 ng/ml) and basic fibroblast growth factor (bFGF, 30 ng/ml). In addition, β-eudesmol at the concentration of 100 μM also had a blocking effect on the phosphorylation of cAMP response element binding protein (CREB) triggered by VEGF 30 ng/ml in HUVEC. β-Eudesmol at the concentration ranging from 10 to 100 μM suppressed proliferation of HeLa, SGC-7901, and BEL-7402 tumor cells in a time-and dose-dependent manner. Moreover, treatment with β-eudesmol (2.5–5 mg/kg) markedly suppressed the growth of H22 and S180 mouse tumor growth in vivo [
59]. Pheochromocytoma mainly refers to a neuroendocrine tumor of the adrenal glands. β-Eudesmol could induce neurite extension in rat pheochromocytoma cells (PC-12), accompanying with inhibition of [
3H] thymidine incorporation. Meanwhile, β-eudesmol also stimulated the improvement of [Ca
2+]. Moreover, β-eudesmol concentration-dependently led to an accumulation of inositol phosphates, and β-eudesmol could increase the p-MAPK time-dependently [
60]. Recently, β-eudesmol was reported to modify the sensitivity of diabetic mice to depolarizing blockers so as to increase the susceptibility to these compounds. By investigating phrenic nerve-diaphragm muscles in normal and alloxan-diabetic mice, β-eudesmol exhibited the potentiating/promoting effect on neuromuscular blockade. Pretreatment with β-eudesmol enhanced the blocking action of succinylcholine to a greater degree in diabetic muscles than in normal ones. 30-min pretreatment in normal muscles could make the effect saturated,while 60-min pretreatment in diabetic muscles could make further potentiation [
61]. It was reported that β-eudesmol could block the nicotinic acetylcholine receptor (nAChR) channel in both open and closed conformations, resulting in potentiating the neuromuscular blockade induced by succinylcholine (SuCh). The blocking effect of SuCh (0.1–10 μM) with β-eudesmol on nAChR channel activity was investigated by using the cell-attached patch clamp technique. Pretreatment with β-eudesmol (20 μM) had no effect on resting membrane potential and ACh-activated channel activities. β-Eudesmol decreased SuCh (above 0.3 μM)-induced prolongation of channel open time and reduced the frequency of channel opening in the presence of SuCh (above 3 μM) in ACh-activated channel currents regulated by SuCh [
62]. β-Eudesmol could potentiate the effect of phenylene-polymethylene-bis-ammonium (PMBA) derivatives on neuromuscular blockades in alloxan-diabetic mice [
63]. Current study manifested that the intragastric injection of β-eudesmol to rats could inhibit efferent adrenal sympathetic nerve activity (ASNA). The knock-out of TRPA1 could block the inhibitory effect of β-eudesmol on ASNA, and subdiaphragmatic vagotomy could promote the suppression of β-eudesmol on ASNA, suggesting that β-eudesmol could modulate ASNA through TRPA1 and afferent vagus nerve [
7]. It was reported that β-eudesmol had the ability of modifying the chemical composition of the workers cuticle, to impair nestmate recognition, initiate alarm behavior and result in nestmate aggression [
64]. Recent study showed that β-eudesmol pre-treatment on mouse diaphragm muscles for 30–60 min could promote [Ca
2+] and twitch tension induced by succinylcholine as nicotinic acetylcholine receptor channel [
65].